Cancer immunotherapy

Source: Wikipedia, the free encyclopedia.

Cancer immunotherapy
immuno-oncology
]

Cancer immunotherapy (immuno-oncotherapy) is the stimulation of the immune system to treat cancer, improving the immune system's natural ability to fight the disease.[1] It is an application of the fundamental research of cancer immunology (immuno-oncology) and a growing subspecialty of oncology.

Cancer immunotherapy exploits the fact that

gastric cancer react well to the approach whereas immunotherapy is not effective for other subtypes.[2]

In 2018, American immunologist James P. Allison and Japanese immunologist Tasuku Honjo received the Nobel Prize in Physiology or Medicine for their discovery of cancer therapy by inhibition of negative immune regulation.[3]

History

"During the 17th and 18th centuries, various forms of immunotherapy in cancer became widespread... In the 18th and 19th centuries, septic dressings enclosing ulcerative tumours were used for the treatment of cancer. Surgical wounds were left open to facilitate the development of infection, and purulent sores were created deliberately... One of the most well-known effects of microorganisms on ... cancer was reported in 1891, when an American surgeon, William Coley, inoculated patients having inoperable tumours with [ Streptococcus pyogenes ]."[4] "Coley [had] thoroughly reviewed the literature available at that time and found 38 reports of cancer patients with accidental or iatrogenic feverish erysipelas. In 12 patients, the sarcoma or carcinoma had completely disappeared; the others had substantially improved. Coley decided to attempt the therapeutic use of iatrogenic erysipelas..."[5] "Coley developed a toxin that contained heat-killed bacteria [ Streptococcus pyogenes and Serratia marcescens ]. Until 1963, this treatment was used for the treatment of sarcoma."[4] "Coley injected more than 1000 cancer patients with bacteria or bacterial products."[6] 51.9% of [Coley's] patients with inoperable soft-tissue sarcomas showed complete tumour regression and survived for more than 5 years, and 21.2% of the patients had no clinical evidence of tumour at least 20 years after this treatment..."[4] Research continued in the 20th century under Maria O'Connor Hornung at Tulane Medical School[7][8]

Types and categories

There are several types of immunotherapy used to treat cancer:[9]

CAR-T cells, and targeted antibody therapies. In contrast, passive immunotherapy does not directly target tumor cells, but enhances the ability of the immune system to attack cancer cells. Examples include checkpoint inhibitors and cytokines
.

Active cellular therapies aim to destroy cancer cells by recognition of distinct markers known as

genetically engineered to recognize tumor-specific antigens, and returned to the patient. Cell types that can be used in this way are natural killer (NK) cells, lymphokine-activated killer cells, cytotoxic T cells, and dendritic cells. Finally, specific antibodies can be developed that recognize cancer cells and target them for destruction by the immune system. Examples of such antibodies include rituximab (targeting CD-20), trastuzumab (targeting HER-2), and cetuximab
(targeting EGFR).

Passive antibody therapies aim to increase the activity of the immune system without specifically targeting cancer cells. For example, cytokines directly stimulate the immune system and increase immune activity. Checkpoint inhibitors target proteins (immune checkpoints) that normally dampen the immune response. This enhances the ability of the immune system to attack cancer cells. Current research is identifying new potential targets to enhance immune function. Approved checkpoint inhibitors include antibodies such as ipilimumab, nivolumab, and pembrolizumab.

Cellular immunotherapy

Dendritic cell therapy

Blood cells are removed from the body, incubated with tumour antigen(s), and activated. Mature dendritic cells are returned to the original cancer-bearing donor to induce an immune response.

Dendritic cell therapy provokes anti-tumor responses by causing dendritic cells to present tumor antigens to lymphocytes, which activates them, priming them to kill other cells that present the antigen. Dendritic cells are antigen-presenting cells (APCs) in the mammalian immune system.[13] In cancer treatment, they aid cancer antigen targeting.[14] The only approved cellular cancer therapy based on dendritic cells is sipuleucel-T.

One method of inducing dendritic cells to present tumor antigens is by vaccination with autologous tumor lysates

granulocyte-macrophage colony-stimulating factor (GM-CSF). The most common sources of antigens used for dendritic cell vaccine in glioblastoma (GBM) as an aggressive brain tumor were whole tumor lysate, CMV antigen RNA and tumor-associated peptides like EGFRvIII.[16]

Dendritic cells can also be activated in vivo by making tumor cells express GM-CSF. This can be achieved by either genetically engineering tumor cells to produce GM-CSF or by infecting tumor cells with an oncolytic virus that expresses GM-CSF.

Another strategy is to remove dendritic cells from the blood of a patient and activate them outside the body. The dendritic cells are activated in the presence of tumor antigens, which may be a single tumor-specific peptide/protein or a tumor

cell lysate
(a solution of broken-down tumor cells). These cells (with optional adjuvants) are infused and provoke an immune response.

Dendritic cell therapies include the use of antibodies that bind to receptors on the surface of dendritic cells. Antigens can be added to the antibody and can induce the dendritic cells to mature and provide immunity to the tumor. Dendritic cell receptors such as

CD40 have been used as antibody targets.[14] Dendritic cell-NK cell interface also has an important role in immunotherapy. The design of new dendritic cell-based vaccination strategies should also encompass NK cell-stimulating potency. It is critical to systematically incorporate NK cells monitoring as an outcome in antitumor DC-based clinical trials.[citation needed
]

Drugs

Sipuleucel-T (Provenge) was approved for treatment of asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer in 2010. The treatment consists of removal of antigen-presenting cells from blood by leukapheresis and growing them with the fusion protein PA2024 made from GM-CSF and prostate-specific prostatic acid phosphatase (PAP) and reinfused. This process is repeated three times.[17][18][19][20]

Adoptive T-cell therapy

Cancer specific T-cells can be obtained by fragmentation and isolation of tumour infiltrating lymphocytes, or by genetically engineering cells from peripheral blood. The cells are activated and grown prior to transfusion into the recipient (tumor bearer).

Adoptive T cell therapy is a form of

tumor infiltrating lymphocytes (TILs). They are activated by the presence of APCs such as dendritic cells that present tumor antigens. Although these cells can attack the tumor, the environment within the tumor is highly immunosuppressive, preventing immune-mediated tumour death.[21]

Multiple ways of producing and obtaining tumour targeted T-cells have been developed. T-cells specific to a tumor antigen can be removed from a tumor sample (TILs) or filtered from blood. Subsequent activation and culturing is performed ex vivo, with the results reinfused. Activation can take place through gene therapy, or by exposing the T cells to tumor antigens.

As of 2014, multiple ACT clinical trials were underway.[22][23][24][25][26] Importantly, one study from 2018 showed that clinical responses can be obtained in patients with metastatic melanoma resistant to multiple previous immunotherapies.[27]

The first 2 adoptive T-cell therapies, tisagenlecleucel and axicabtagene ciloleucel, were approved by the FDA in 2017.[28][29]

Another approach is adoptive transfer of haploidentical

GVHD. The disadvantage is frequently impaired function of the transferred cells.[31]

CAR-T cell therapy

Main article:
Chimeric antigen receptor

The premise of CAR-T immunotherapy is to modify T cells to recognize cancer cells in order to target and destroy them. Scientists harvest T cells from people, genetically alter them to add a chimeric antigen receptor (CAR) that specifically recognizes cancer cells, then infuse the resulting CAR-T cells into patients to attack their tumors.

Approved drugs

chimeric antigen receptor (CAR-T) therapy, was approved by FDA in 2017 to treat acute lymphoblastic leukemia (ALL).[32] This treatment removes CD19
positive cells (B-cells) from the body (including the diseased cells, but also normal antibody-producing cells).

Axicabtagene ciloleucel (Yescarta) is another CAR-T therapeutic, approved in 2017 for treatment of diffuse large B-cell lymphoma (DLBCL).[29]

T cell receptor T cell therapy

Main article: T cell receptor T cell therapy

TCR-T therapies use heterodimers made of alpha and beta peptide chains to recognize MHC-presented polypeptide fragments molecules. Unlike CAR-T's cell surface antigens, TCR-T can recognize that larger set of intracellular antigen fragments. However, TCR-T cell therapy depends on MHC molecules, limiting its usefulness.[33]

Multifunctional alginate scaffolds for T cell engineering and release

Multifunctional alginate scaffolds for T cell engineering and release (MASTER) is a technique for in situ engineering, replication and release of genetically engineered T cells. It is an evolution of

interleukins that trigger cell proliferation. The MASTER is then implanted into the patient. The activated T cells interact with the viruses to become CAR T cells. The interleukins stimulate these CAR T cells to proliferate, and the CAR T cells exit the MASTER to attack the cancer. The technique takes hours instead of weeks. And because the cells are younger, they last longer in the body, show stronger potency against cancer, and display fewer markers of exhaustion. These features were demonstrated in mouse models. The treatment was more effective and longer lasting against lymphoma.[34][35]

Antibody therapy

Many forms of antibodies can be engineered.
This paragraph is an excerpt from Monoclonal antibody therapy.[edit]
Each antibody binds only one specific antigen.
cytotoxic
radiation).

Antibody types

Conjugation

Two types are used in cancer treatments:[37]

  • Naked monoclonal antibodies are antibodies without added elements. Most antibody therapies use this antibody type.
  • Conjugated monoclonal antibodies are joined to another molecule, which is either cytotoxic or
    radioactive. The toxic chemicals are those typically used as chemotherapy drugs, but other toxins can be used. The antibody binds to specific antigens on cancer cell surfaces, directing the therapy to the tumor. Radioactive compound-linked antibodies are referred to as radiolabelled. Chemolabelled or immunotoxins antibodies are tagged with chemotherapeutic molecules or toxins, respectively.[38] Research has also demonstrated conjugation of a TLR agonist to an anti-tumor monoclonal antibody.[39]

Fc regions

Fc's ability to bind

CD40 require engagement with selective Fc receptors for optimal therapeutic efficacy.[44] Together, these studies underscore the importance of Fc status in antibody-based immune checkpoint
targeting strategies.

Human/non-human antibodies

Antibodies can come from a variety of sources, including human cells, mice, and a combination of the two (chimeric antibodies). Different sources of antibodies can provoke different kinds of immune responses. For example, the human immune system can recognize mouse antibodies (also known as murine antibodies) and trigger an immune response against them. This could reduce the effectiveness of the antibodies as a treatment and cause an immune reaction. Chimeric antibodies attempt to reduce murine antibodies'

variable regions are derived from murine sources. Human antibodies have been produced using unmodified human DNA.[38]

Antibody-dependent cell-mediated cytotoxicity. When the Fc receptors on natural killer (NK) cells interact with Fc regions of antibodies bound to cancer cells, the NK cell releases perforin and granzyme, leading to cancer cell apoptosis.

Mechanism of action

Antibody-dependent cell-mediated cytotoxicity (ADCC)

perforin and granzyme B to kill the tumor cell. Examples include rituximab, ofatumumab, elotuzumab, and alemtuzumab. Antibodies under development have altered Fc regions that have higher affinity for a specific type of Fc receptor, FcγRIIIA, which can dramatically increase effectiveness.[45][46]

Anti-CD47 therapy

Many tumor cells overexpress

antibodies, engineered decoy receptors, anti-SIRPα antibodies and bispecific agents.[48] As of 2017, wide range of solid and hematologic malignancies were being clinically tested.[48][50]

Anti-GD2 antibodies

The GD2 ganglioside

Carbohydrate

soft tissue sarcomas. It is not usually expressed on the surface of normal tissues, making it a good target for immunotherapy. As of 2014, clinical trials were underway.[51]

Complement Activation

The

antibody-dependent cell-mediated cytotoxicity; and CR3-dependent cellular cytotoxicity. Complement-dependent cytotoxicity occurs when antibodies bind to the cancer cell surface, the C1 complex binds to these antibodies and subsequently, protein pores are formed in cancer cell membrane.[52]

Blocking

Antibody therapies can also function by binding to proteins and physically blocking them from interacting with other proteins. Checkpoint inhibitors (CTLA-4, PD-1, and PD-L1) operate by this mechanism. Briefly, checkpoint inhibitors are proteins that normally help to slow immune responses and prevent the immune system from attacking normal cells. Checkpoint inhibitors bind these proteins and prevent them from functioning normally, which increases the activity of the immune system. Examples include durvalumab, ipilimumab, nivolumab, and pembrolizumab.

FDA-approved antibodies

Cancer immunotherapy:Monoclonal antibodies[37][53]
Antibody Brand name Type Target Approval date Approved treatment(s)
Alemtuzumab Campath humanized CD52 2001
B-cell chronic lymphocytic leukemia (CLL)[54]
Atezolizumab Tecentriq humanized PD-L1 2016 bladder cancer[55]
Avelumab Bavencio human PD-L1 2017 metastatic Merkel cell carcinoma[56]
Ipilimumab Yervoy human
CTLA4
 2011 metastatic melanoma[57]
Elotuzumab Empliciti humanized SLAMF7 2015 multiple myeloma[58]
Ofatumumab Arzerra human CD20 2009 refractory
CLL[59]
Nivolumab Opdivo human
PD-1
 2014
squamous non-small cell lung cancer, Renal cell carcinoma, colorectal cancer, hepatocellular carcinoma, classical hodgkin lymphoma[60][61]
Pembrolizumab Keytruda humanized
PD-1
 2014
Hodgkin's lymphoma,[63] Merkel-cell carcinoma (MCC),[64] primary mediastinal B-cell lymphoma (PMBCL),[65] stomach cancer, cervical cancer[66]
Rituximab Rituxan, Mabthera chimeric CD20 1997 non-Hodgkin lymphoma[67]
Durvalumab Imfinzi human PD-L1 2017 bladder cancer[68] non-small cell lung cancer[69]

Alemtuzumab

myelosuppression.[70][71][72]

Durvalumab

Main article: Durvalumab

Durvalumab (Imfinzi) is a human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody that blocks the interaction of programmed cell death ligand 1 (PD-L1) with the PD-1 and CD80 (B7.1) molecules. Durvalumab is approved for the treatment of patients with locally advanced or metastatic urothelial carcinoma who:

  • have disease progression during or following platinum-containing chemotherapy.
  • have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

On 16 February 2018, the Food and Drug Administration approved durvalumab for patients with unresectable stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy.[73]

Ipilimumab

CTLA4. In normal physiology T-cells are activated by two signals: the T-cell receptor binding to an antigen-MHC complex and T-cell surface receptor CD28 binding to CD80 or CD86 proteins. CTLA4 binds to CD80 or CD86, preventing the binding of CD28 to these surface proteins and therefore negatively regulates the activation of T-cells.[74][75][76][77]

Active

cytotoxic T-cells are required for the immune system to attack melanoma cells. Normally inhibited active melanoma-specific cytotoxic T-cells can produce an effective anti-tumor response. Ipilimumab can cause a shift in the ratio of regulatory T-cells to cytotoxic T-cells to increase the anti-tumor response. Regulatory T-cells inhibit other T-cells, which may benefit the tumor.[74][75][76][77]

Nivolumab

Main article:
IgG4 antibody that prevents T-cell inactivation by blocking the binding of programmed cell death 1 ligand 1 or programmed cell death 1 ligand 2 (PD-L1 or PD-L2), a protein expressed by cancer cells, with PD-1, a protein found on the surface of activated T-cells.[78][79] Nivolumab is used in advanced melanoma, metastatic renal cell carcinoma, advanced lung cancer, advanced head and neck cancer, and Hodgkin's lymphoma.[80]

Ofatumumab

IgG1 antibody that binds to CD20. It is used in the treatment of chronic lymphocytic leukemia (CLL) because the cancerous cells of CLL are usually CD20-expressing B-cells. Unlike rituximab, which binds to a large loop of the CD20 protein, ofatumumab binds to a separate, small loop. This may explain their different characteristics. Compared to rituximab, ofatumumab induces complement-dependent cytotoxicity at a lower dose with less immunogenicity.[81][82]

Pembrolizumab

As of 2019,

urothelial carcinoma, stomach cancer and cervical cancer.[85]

Rituximab

Ibritumomab. As with ibritumomab, rituximab targets CD20, making it effective in treating certain B-cell malignancies. These include aggressive and indolent lymphomas such as diffuse large B-cell lymphoma and follicular lymphoma and leukemias such as B-cell chronic lymphocytic leukemia. Although the function of CD20 is relatively unknown, CD20 may be a calcium channel involved in B-cell activation. The antibody's mode of action is primarily through the induction of ADCC and complement-mediated cytotoxicity. Other mechanisms include apoptosis[clarification needed] and cellular growth arrest. Rituximab also increases the sensitivity of cancerous B-cells to chemotherapy.[86][87][88][89][90]

Immune checkpoint antibody therapy or immune checkpoint blockade

Main articles: Immune checkpoint and Immunotherapy
Immune checkpoints in the tumour microenvironment
Cancer therapy by inhibition of negative immune regulation (CTLA4, PD1)

Immune checkpoints affect the immune system function. Immune checkpoints can be stimulatory or inhibitory. Tumors can use these checkpoints to protect themselves from immune system attacks. Checkpoint therapies approved as of 2012 block inhibitory checkpoint receptors. Blockade of negative feedback signaling to immune cells thus results in an enhanced immune response against tumors.[79] As of 2020, immune checkpoint blockade therapies have varied effectiveness. In Hodgkin lymphoma and natural killer T-cell lymphoma, response rates are high, at 50–60%. Response rates are quite low for breast and prostate cancers, however.[91]

One ligand-receptor interaction under investigation is the interaction between the transmembrane

PD-1 ligand 1 (PD-L1, CD274). PD-L1 on the cell surface binds to PD1 on an immune cell surface, which inhibits immune cell activity. Among PD-L1 functions is a key regulatory role on T cell activities. It appears that (cancer-mediated) upregulation of PD-L1 on the cell surface may inhibit T cells that might otherwise attack. PD-L1 on cancer cells also inhibits FAS- and interferon-dependent apoptosis, protecting cells from cytotoxic molecules produced by T cells. Antibodies that bind to either PD-1 or PD-L1 and therefore block the interaction may allow the T-cells to attack the tumor.[92]

CTLA-4 blockade

The first checkpoint antibody approved by the FDA was

PD-L1 inhibitors is tested on different types of cancer.[96]

However, as of 2015 it is known that patients treated with checkpoint blockade (specifically CTLA-4 blocking antibodies), or a combination of check-point blocking antibodies, are at high risk of having immune-related adverse events such as dermatologic, gastrointestinal, endocrine, or hepatic autoimmune reactions.[78] These are most likely due to the breadth of the induced T-cell activation when anti-CTLA-4 antibodies are administered by injection in the bloodstream.

A 2024 cohort study of ICI use during pregnancy showed no overreporting of specific adverse effects on pregnancy, fetal, and/or newborn outcomes, interestingly.[97]

Using a mouse model of bladder cancer, researchers have found that a local injection of a low dose anti-CTLA-4 in the tumour area had the same tumour inhibiting capacity as when the antibody was delivered in the blood.[98] At the same time the levels of circulating antibodies were lower, suggesting that local administration of the anti-CTLA-4 therapy might result in fewer adverse events.[98]

PD-1 inhibitors

Main article: PD-1 and PD-L1 inhibitors

Initial clinical trial results with IgG4 PD1 antibody

Hodgkin's lymphoma.[99] A 2016 clinical trial for non-small cell lung cancer failed to meet its primary endpoint for treatment in the first line setting, but is FDA approved in subsequent lines of therapy.[100]

Pembrolizumab (Keytruda) is another PD1 inhibitor that was approved by the FDA in 2014. Pembrolizumab is approved to treat melanoma and lung cancer.[99]

Antibody

BGB-A317 is a PD-1 inhibitor (designed to not bind Fc gamma receptor I) in early clinical trials.[101]

PD-L1 inhibitors

Main article: PD-1 and PD-L1 inhibitors

In May 2016, PD-L1 inhibitor atezolizumab[102] was approved for treating bladder cancer.

Anti-PD-L1 antibodies currently in development include avelumab[103] and durvalumab,[104] in addition to an inhibitory affimer.[105]

CISH

Other modes of enhancing [adoptive] immuno-therapy include targeting so-called

CISH. Many cancer patients do not respond to immune checkpoint blockade. Response rate may be improved by combining immune checkpoint blockade with additional rationally selected anticancer therapies, including those that stimulate T cell infiltration. For example, targeted therapies such as radiotherapy, vasculature targeting agents, and immunogenic chemotherapy[106]
can improve immune checkpoint blockade response in animal models.

Combining various immunotherapies such as PD1 and CTLA4 inhibitors can enhance anti-tumor response leading to durable responses.[107][108]

Combinatorial ablation and immunotherapy enhances the immunostimulating response and has synergistic effects for curative metastatic cancer treatment.[109]

Combining checkpoint immunotherapies with pharmaceutical agents has the potential to improve response, and as of 2018 were a highly investigated area of clinical investigation.[110] Immunostimulatory drugs such as CSF-1R inhibitors and TLR agonists have been particularly effective in this setting.[111][112]

Cytokine therapy

Cytokines are proteins produced by many types of cells present within a tumor. They can modulate immune responses. The tumor often employs them to allow it to grow and reduce the immune response. These immune-modulating effects allow them to be used as drugs to provoke an immune response. Two commonly used cytokines are interferons and interleukins.[113]

malignant melanoma and renal cell carcinoma.[114]

Interferon

animal models.[115][116]

Unlike type I IFNs,

ovarian carcinoma. The in vitro study of IFN-gamma in cancer cells is more extensive and results indicate anti-proliferative activity of IFN-gamma leading to the growth inhibition or cell death, generally induced by apoptosis but sometimes by autophagy.[117]

Interleukin

malignant melanoma and renal cell carcinoma. In normal physiology it promotes both effector T cells and T-regulatory cells, but its exact mechanism of action is unknown.[113][118]

Genetic pre-treatment testing for therapeutic significance

Because of the high cost of many of immunotherapy medications and the reluctance of medical insurance companies to prepay for their prescriptions various test methods have been proposed, to attempt to forecast the effectiveness of these medications. In some cases the FDA has approved genetic tests for medication specific to certain genetic markers. For example, the FDA approved BRAF associated medication for metastatic melanoma, to be administered to patients after testing for the BRAF genetic mutation.[119]

As of 2018, the detection of PD-L1 protein seemed to be an indication of cancer susceptible to several immunotherapy medications, but research found that both the lack of this protein or its inclusion in the cancerous tissue was inconclusive, due to the little-understood varying quantities of the protein during different times and locations within the infected cells and tissue.[120][121][122]

In 2018, some genetic indications such as Tumor Mutational Burden (TMB, the number of mutations within a targeted genetic region in the cancerous cell's DNA), and microsatellite instability (MSI, the quantity of impaired DNA mismatch leading to probable mutations), have been approved by the FDA as good indicators for the probability of effective treatment of immunotherapy medication for certain cancers, but research is still in progress.[123][124] As of 2020, the patient prioritization for immunotherapy based on TMB was still highly controversial.[125][126]

Tests of this sort are being widely advertised for general cancer treatment and are expensive. In the past, some genetic testing for cancer treatment has been involved in scams such as the Duke University Cancer Fraud scandal, or claimed to be hoaxes.[127][128][129]

Research

Further information on the Autologous Lymphoid Effector Cells Specific Against Tumor cells technology: ALECSAT


Oncolytic virus

An

oncolysis, they release new infectious virus particles or virions to help destroy the remaining tumour. Oncolytic viruses are thought not only to cause direct destruction of the tumour cells, but also to stimulate host anti-tumour immune responses for long-term immunotherapy.[130][131][132]

The potential of viruses as anti-cancer agents was first realized in the early twentieth century, although coordinated research efforts did not begin until the 1960s. A number of viruses including

Newcastle disease virus and vaccinia have now been clinically tested as oncolytic agents. T-Vec is the first FDA-approved oncolytic virus for the treatment of melanoma. A number of other oncolytic viruses are in Phase II-III development.[133]

Polysaccharides

Certain compounds found in

cytokines and have been investigated in clinical trials as immunologic adjuvants.[134]

Neoantigens

Main article:
Neoantigen

Many tumors express mutations. These mutations potentially create new targetable antigens (neoantigens) for use in T-cell immunotherapy. The presence of CD8+ T cells in cancer lesions, as identified using RNA sequencing data, is higher in tumors with a high mutational burden. The level of transcripts associated with the cytolytic activity of natural killer cells and T cells positively correlates with mutational load in many human tumors. In non–small cell lung cancer patients treated with lambrolizumab, mutational load shows a strong correlation with clinical response. In melanoma patients treated with ipilimumab, the long-term benefit is also associated with a higher mutational load, although less significantly. The predicted MHC binding neoantigens in patients with a long-term clinical benefit were enriched for a series of tetrapeptide motifs that were not found in tumors of patients with no or minimal clinical benefit.[135] However, human neoantigens identified in other studies do not show the bias toward tetrapeptide signatures.[136]

Polysaccharide-K

In the 1980s, Japan's

Coriolus versicolor, to stimulate the immune systems of patients undergoing chemotherapy. It is a dietary supplement in the US and other jurisdictions.[137]

See also

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External links

  • Association for Immunotherapy of Cancer
    • Retrieved from "https://en.wikipedia.org/w/index.php?title=Cancer_immunotherapy&oldid=1220108270"