Chemoimmunotherapy

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Chemoimmunotherapy is chemotherapy combined with immunotherapy. Chemotherapy uses different drugs to kill or slow the growth of cancer cells; immunotherapy uses treatments to stimulate or restore the ability of the immune system to fight cancer. [1] A common chemoimmunotherapy regimen is CHOP combined with rituximab (CHOP-R) for B-cell non-Hodgkin lymphomas.

Contents

Cancer treatment has progressed to combine different methods to improve the chances of survival. Surgery and radiation therapy are used to control cancer in specific areas, while systemic therapies (such as chemotherapy, endocrine therapy, targeted therapies, and bisphosphonates) are used to manage widespread cancer or cancer that has spread from its original site. [2] Combining different therapies, including multiple drugs with complementary effects, has become common. This approach has been shown to improve five-year survival rates and delay the return of tumors.

Chemotherapy

In the early 1900s, German chemist Paul Ehrlich began creating drugs for infectious diseases and introduced the term "chemotherapy" for using chemicals to treat illnesses. He was also the first to use animal models to test the effectiveness of these chemicals, significantly advancing cancer drug development. [3] During World War II, the Cancer Chemotherapy National Service Center was set up to develop new drugs. [4] Successes in treating acute childhood leukemia and advanced Hodgkin's disease led to increased screening for anti-tumor chemicals. It was discovered that combining different drugs improved treatment outcomes. Initially, the idea that chemicals could kill cancer cells and lead to cancer-specific therapies was not considered possible.

Immunotherapy

James Allison, now at the University of Texas MD Anderson Cancer Center, was an early pioneer of immunotherapy. He discovered that CTLA-4 inhibits T cells from fully attacking, and hypothesized that blocking CTLA-4 could unleash the immune system to fight cancer. Initially, his idea was met with skepticism, but he continued his research and proved its validity in mice. Clinical trials later showed that anti-CTLA-4 antibodies could extend the lives of patients with metastatic melanoma by four months, and anti-PD-1 antibodies also demonstrated anti-tumor effects. [5] Using the immune system to combat cancer has since gained popularity.

However, the interaction between tumors and the immune system creates multiple mechanisms of regulation and immune escape that suppress the immune response to tumors. Various immune cells, such as regulatory T cells (Tregs), T helper cells producing interleukin-17, myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages (TAMs), promote tumor growth and inhibit the immune response. Additionally, the tumor microenvironment further suppresses the anti-tumor immune response with high levels of suppressive cytokines (TGF-β, TNF, IL-10), expression of immune checkpoint molecules (PD-L1, B7-H4), and other alterations that help the tumor evade the immune system, such as the loss of tumor antigens necessary for antigen processing and presentation. [3]

Crosstalk between chemotherapy and immunotherapy

Chemotherapy is often seen as immunosuppressive because it suppresses immune cell production in the bone marrow in a dose-dependent manner. This suggests it might conflict with immunotherapy. However, research shows that certain chemotherapy drugs can, under specific conditions, boost the immune response against tumors and enhance the effectiveness of immunotherapy. [6]

Chemotherapy can boost tumor immunity in two main ways: (a) by killing cancer cells through immunogenic cell death, and (b) by affecting both cancerous and normal cells in the tumor environment. Despite this, many chemotherapy treatments can also suppress the immune system by causing lymphopenia or impairing lymphocyte function. Integrating immune-based therapies with chemotherapy has the potential to alter the body's overall environment and the local tumor microenvironment, disrupting immune tolerance and suppression pathways. [3]

Clinical examples

There are several successful examples of the use of chemoimmunotherapy in treating cancer. For diffuse large B-cell lymphoma, the standard treatment includes cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Adding rituximab, a monoclonal antibody targeting the CD20 B-cell antigen, to the CHOP regimen has been shown to improve complete-response rates and extend event-free and overall survival in elderly patients without significantly increasing toxicity. [7]

In metastatic breast cancer overexpressing HER2, chemoimmunotherapy also shows better results. The HER2 gene, which encodes the growth factor receptor HER2, is overexpressed in 25-30% of breast cancers, making tumors more aggressive. Trastuzumab, a monoclonal antibody against HER2, added to chemotherapy, has been proven in clinical trials to extend the time to disease progression, increase response rates, prolong response duration, reduce the death rate at 1 year, improve overall survival, and lower the risk of death by 20%. This demonstrates trastuzumab's significant benefit when combined with first-line chemotherapy for HER2-positive metastatic breast cancer. [8]

Related Research Articles

Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as activation immunotherapies, while immunotherapies that reduce or suppress are classified as suppression immunotherapies. Immunotherapy is under preliminary research for its potential to treat various forms of cancer.

A cancer vaccine, or oncovaccine, is a vaccine that either treats existing cancer or prevents development of cancer. Vaccines that treat existing cancer are known as therapeutic cancer vaccines or tumor antigen vaccines. Some of the vaccines are "autologous", being prepared from samples taken from the patient, and are specific to that patient.

<span class="mw-page-title-main">Rituximab</span> Biopharmaceutical drug

Rituximab, sold under the brand name Rituxan among others, is a monoclonal antibody medication used to treat certain autoimmune diseases and types of cancer. It is used for non-Hodgkin lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis, idiopathic thrombocytopenic purpura, pemphigus vulgaris, myasthenia gravis and Epstein–Barr virus-positive mucocutaneous ulcers. It is given by slow intravenous infusion.

<span class="mw-page-title-main">Cancer immunotherapy</span> Artificial stimulation of the immune system to treat cancer

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. It is an application of the fundamental research of cancer immunology (immuno-oncology) and a growing subspecialty of oncology.

<span class="mw-page-title-main">Ibritumomab tiuxetan</span> Radioimmunotherapy treatment

Ibritumomab tiuxetan, sold under the trade name Zevalin, is a monoclonal antibody radioimmunotherapy treatment for non-Hodgkin's lymphoma. The drug uses the monoclonal mouse IgG1 antibody ibritumomab in conjunction with the chelator tiuxetan, to which a radioactive isotope is added. Tiuxetan is a modified version of DTPA whose carbon backbone contains an isothiocyanatobenzyl and a methyl group.

<span class="mw-page-title-main">Targeted therapy</span> Type of therapy

Targeted therapy or molecularly targeted therapy is one of the major modalities of medical treatment (pharmacotherapy) for cancer, others being hormonal therapy and cytotoxic chemotherapy. As a form of molecular medicine, targeted therapy blocks the growth of cancer cells by interfering with specific targeted molecules needed for carcinogenesis and tumor growth, rather than by simply interfering with all rapidly dividing cells. Because most agents for targeted therapy are biopharmaceuticals, the term biologic therapy is sometimes synonymous with targeted therapy when used in the context of cancer therapy. However, the modalities can be combined; antibody-drug conjugates combine biologic and cytotoxic mechanisms into one targeted therapy.

<span class="mw-page-title-main">Monoclonal antibody therapy</span> Form of immunotherapy

Monoclonal antibodies (mAbs) have varied therapeutic uses. It is possible to create a mAb that binds specifically to almost any extracellular target, such as cell surface proteins and cytokines. They can be used to render their target ineffective, to induce a specific cell signal, to cause the immune system to attack specific cells, or to bring a drug to a specific cell type.

<span class="mw-page-title-main">Ipilimumab</span> Pharmaceutical drug

Ipilimumab, sold under the brand name Yervoy, is a monoclonal antibody medication that works to activate the immune system by targeting CTLA-4, a protein receptor that downregulates the immune system.

<span class="mw-page-title-main">Cancer immunology</span> Study of the role of the immune system in cancer

Cancer immunology (immuno-oncology) is an interdisciplinary branch of biology and a sub-discipline of immunology that is concerned with understanding the role of the immune system in the progression and development of cancer; the most well known application is cancer immunotherapy, which utilises the immune system as a treatment for cancer. Cancer immunosurveillance and immunoediting are based on protection against development of tumors in animal systems and (ii) identification of targets for immune recognition of human cancer.

<span class="mw-page-title-main">Trifunctional antibody</span> Monoclonal antibody

A trifunctional antibody is a monoclonal antibody with binding sites for two different antigens, typically CD3 and a tumor antigen, making it a type of bispecific monoclonal antibody. In addition, its intact Fc-part can bind to an Fc receptor on accessory cells like conventional monospecific antibodies. The net effect is that this type of drug links T cells and monocytes/macrophages, natural killer cells, dendritic cells or other Fc receptor expressing cells to the tumor cells, leading to their destruction.

Gene expression profiling has revealed that diffuse large B-cell lymphoma (DLBCL) is composed of at least 3 different sub-groups, each having distinct oncogenic mechanisms that respond to therapies in different ways. Germinal Center B-Cell like (GCB) DLBCLs appear to arise from normal germinal center B cells, while Activated B-cell like (ABC) DLBCLs are thought to arise from postgerminal center B cells that are arrested during plasmacytic differentiation. The differences in gene expression between GCB DLBCL and ABC DLBCL are as vast as the differences between distinct types of leukemia, but these conditions have historically been grouped together and treated as the same disease.

Urelumab is a fully human, non‐ligand binding, CD137 agonist immunoglobulin‐γ 4 (IgG4) monoclonal antibody. It was developed utilizing Medarex's UltiMAb(R) technology by Bristol-Myers Squibb for the treatment of cancer and solid tumors. Urelumab promotes anti-tumor immunity, or an immune response against tumor cells, via CD137 activation. The application of Urelumab has been limited due to the fact that it can cause severe liver toxicity.

<span class="mw-page-title-main">Nivolumab</span> Anticancer medication

Nivolumab, sold under the brand name Opdivo, is an anti-cancer medication used to treat a number of types of cancer. This includes melanoma, lung cancer, malignant pleural mesothelioma, renal cell carcinoma, Hodgkin lymphoma, head and neck cancer, urothelial carcinoma, colon cancer, esophageal squamous cell carcinoma, liver cancer, gastric cancer, and esophageal or gastroesophageal junction cancer. It is administered intravenously.

<span class="mw-page-title-main">Abscopal effect</span> Hypothesis in the treatment of metastatic cancer

The abscopal effect is a hypothesis in the treatment of metastatic cancer whereby shrinkage of untreated tumors occurs concurrently with shrinkage of tumors within the scope of the localized treatment. R.H. Mole proposed the term "abscopal" in 1953 to refer to effects of ionizing radiation "at a distance from the irradiated volume but within the same organism".

Photoimmunotherapy (PIT) is an oncological treatment that combines photodynamic therapy of tumor with immunotherapy treatment. Combining photodynamic therapy with immunotherapy enhances the immunostimulating response and has synergistic effects for metastatic cancer treatment.

<span class="mw-page-title-main">Pembrolizumab</span> Pharmaceutical drug used in cancer treatment

Pembrolizumab, sold under the brand name Keytruda, is a humanized antibody, more specifically a PD-1 Inhibitor, used in cancer immunotherapy that treats melanoma, lung cancer, head and neck cancer, Hodgkin lymphoma, stomach cancer, cervical cancer, and certain types of breast cancer. It is administered by slow intravenous injection.

<span class="mw-page-title-main">PD-1 and PD-L1 inhibitors</span> Class of anticancer drugs

PD-1 inhibitors and PD-L1 inhibitors are a group of checkpoint inhibitor anticancer drugs that block the activity of PD-1 and PDL1 immune checkpoint proteins present on the surface of cells. Immune checkpoint inhibitors are emerging as a front-line treatment for several types of cancer.

This is a historical timeline of the development and progress of cancer treatments, which includes time of discovery, progress, and approval of the treatments.

Checkpoint inhibitor therapy is a form of cancer immunotherapy. The therapy targets immune checkpoints, key regulators of the immune system that when stimulated can dampen the immune response to an immunologic stimulus. Some cancers can protect themselves from attack by stimulating immune checkpoint targets. Checkpoint therapy can block inhibitory checkpoints, restoring immune system function. The first anti-cancer drug targeting an immune checkpoint was ipilimumab, a CTLA4 blocker approved in the United States in 2011.

Passive antibody therapy, also called serum therapy, is a subtype of passive immunotherapy that administers antibodies to target and kill pathogens or cancer cells. It is designed to draw support from foreign antibodies that are donated from a person, extracted from animals, or made in the laboratory to elicit an immune response instead of relying on the innate immune system to fight disease. It has a long history from the 18th century for treating infectious diseases and is now a common cancer treatment. The mechanism of actions include: antagonistic and agonistic reaction, complement-dependent cytotoxicity (CDC), and antibody-dependent cellular cytotoxicity (ADCC).

References

  1. ↑ "Definition of chemoimmunotherapy". NCI Dictionary of Cancer Terms. U.S. National Institutes of Health. One or more of the preceding sentences incorporates text from these sources, which are in the public domain :National Cancer Institute
  2. ↑ Emens LA (2010). "Chemoimmunotherapy". Cancer Journal. 16 (4): 295–303. doi:10.1097/PPO.0b013e3181eb5066. PMC   2919833 . PMID   20693839.
  3. 1 2 3 Chen G, Emens LA (February 2013). "Chemoimmunotherapy: reengineering tumor immunity". Cancer Immunology, Immunotherapy. 62 (2): 203–16. doi:10.1007/s00262-012-1388-0. PMC   3608094 . PMID   23389507.
  4. ↑ DeVita VT, Chu E (November 2008). "A history of cancer chemotherapy". Cancer Research. 68 (21): 8643–53. doi:10.1158/0008-5472.CAN-07-6611. PMID   18974103.
  5. ↑ Couzin-Frankel J (December 2013). "Breakthrough of the year 2013. Cancer immunotherapy". Science. 342 (6165). New York, N.Y.: 1432–3. doi:10.1126/science.342.6165.1432. PMID   24357284.
  6. ↑ Sordo-Bahamonde C, Lorenzo-Herrero S, Gonzalez-Rodriguez AP, Martínez-Pérez A, Rodrigo JP, García-Pedrero JM, et al. (May 2023). "Chemo-Immunotherapy: A New Trend in Cancer Treatment". Cancers. 15 (11): 2912. doi: 10.3390/cancers15112912 . PMC   10252089 . PMID   37296876.
  7. ↑ Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, et al. (January 2002). "CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma". The New England Journal of Medicine. 346 (4): 235–42. doi:10.1056/NEJMoa011795. PMID   11807147.
  8. ↑ Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, et al. (March 2001). "Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2". The New England Journal of Medicine. 344 (11): 783–92. doi:10.1056/NEJM200103153441101. PMID   11248153.
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