Understanding Immunotherapy

Immunotherapy is a medical treatment that leverages the immune system to improve patient outcomes. While the immune system serves as the primary defense against diseases and infections, it can sometimes become either too weak or overly reactive. The concept of immunotherapy emerged to alleviate symptoms associated with illnesses that affect the immune system. This treatment is classified as a biological therapy since it utilizes products derived from living organisms, namely, components of the immune system.

Biological Elements Key to Immunotherapy

The Immune Response Mechanism

The immune system activates when a foreign substance, known as an antigen, enters the body, triggering a series of immune responses.

B Cell and Antibody Response

B cells play a crucial role in identifying antigens and producing specific antibodies. These antibodies bind to their corresponding antigens, marking them for destruction by white blood cells.

T Cell Response

If B cells are unable to respond quickly enough and antigens infect body cells, T cells become essential. Infected cells express antigen proteins on their surfaces, which are recognized by T cells. Killer T cells subsequently target and destroy these infected cells. Both B cells and T cells are integral to the manipulation strategies used in immunotherapy treatments.

Cancer Immunotherapy

Cancer is characterized by the uncontrolled proliferation of the body’s cells, often due to genetic mutations. Immunotherapy aims to enhance the body’s ability to fight cancer.

CAR-T Cell Therapy for Cancer

CAR-T cell therapy involves extracting T cells from cancer patients and modifying their DNA in a laboratory to create chimeric antigen receptors (CAR) that can identify proteins commonly found on tumor cells. These engineered CAR-T cells are then reinfused into the patient, enabling a targeted attack on cancerous cells. Three CAR-T cell therapies have received FDA approval for specific blood cancers, such as leukemia and lymphoma, although side effects like immune over-activation are currently under investigation.

Tumor-Infiltrating Lymphocyte (TIL) Therapy

TIL therapy closely resembles CAR-T cell therapy, but the extracted T cells are not genetically modified. Doctors harvest T cells from the tumor site, cultivate them in a lab, and then reintroduce them to the patient, enhancing the immune response. TIL therapy has been approved for treating metastatic melanoma.

Immune Checkpoint Modulators

Immune checkpoints are regulatory mechanisms that ensure the immune response is appropriate. These checkpoints can be manipulated to treat cancer. A significant checkpoint involves the PD-1 receptor on T cells binding to the PD-L1 protein on human cells. This interaction prevents T cells from attacking healthy cells. However, in cancerous cells, antibodies against PD-1 or PD-L1 can block this binding, enabling T cells to target cancer cells. Monoclonal antibodies produced in the lab are reintroduced into the patient to facilitate this process.

A 2018 study on metastatic melanoma found that patients treated with the anti-PD-1 therapy pembrolizumab showed a complete response in 105 out of 665 participants, with a significant disease-free rate of 90.9% two years after treatment.

Comparative Efficacy of Immune Checkpoint Inhibitors

Another study compared the response rates of advanced melanoma patients treated with pembrolizumab versus ipilimumab, an immune checkpoint inhibitor that blocks the CTLA-4 receptor. The response rate was markedly higher for pembrolizumab at 32.9% compared to 11.9% for ipilimumab. Furthermore, combining nivolumab (anti-PD-1) and ipilimumab resulted in a 58% overall survival rate after three years, compared to 34% for those treated only with ipilimumab, indicating potential benefits of combination therapies.

Cancer Vaccines

Cancer vaccines represent another innovative treatment approach, with two vaccines currently available: T-VEC for melanoma and sipuleucel-T.

Sipuleucel-T

Approved in 2010 for late-stage prostate cancer, sipuleucel-T enhances immune response by targeting dendritic cells, which play a role in T cell activation against cancer cells. A study involving 336 patients with metastatic castrate-resistant prostate cancer treated with sipuleucel-T revealed a survival rate of 79% at 36 months, indicating its potential to delay disease progression.

Immunotherapy for Autoimmune Diseases

In cases of autoimmune diseases, the immune system mistakenly attacks healthy cells. Immunotherapy can help to downregulate this inappropriate immune response.

Type I Diabetes

In type I diabetes, the immune system targets insulin-producing islet cells. A study on patients receiving islet cell transplants alongside monoclonal antibody treatment found that this approach led to five-year insulin independence, suggesting a reduction in immune attacks on islet cells.

Rheumatoid Arthritis

A 2019 study on patients with rheumatoid arthritis assessed the impact of monoclonal antibodies on cardiovascular inflammation, demonstrating significant reductions in inflammation due to the immunotherapy.

Other autoimmune diseases with available immunotherapy treatments include psoriasis, multiple sclerosis, and Crohn’s disease.

Immunotherapy for Allergies

Immunotherapy can also be effective in treating non-food allergies through allergen shots. These shots introduce small amounts of allergens to the immune system, prompting it to build up antibodies. Initial treatments occur one to two times per week for three to six months, gradually increasing the allergen dose. This method has demonstrated improvements in allergic asthma, insect sting allergies, and allergic rhinitis, and may prevent rhinitis from progressing to asthma.

The Future of Immunotherapy

With promising results emerging for cancers and autoimmune diseases, further research is underway to broaden the applications of immunotherapy. Solid tumors have yet to respond effectively to CAR-T cell therapy, and ongoing clinical trials are exploring combination therapies for mismatch repair proficient colorectal cancer. Researchers are also focused on minimizing side effects for cancer patients undergoing organ transplants.

If you have a health condition that could benefit from immunotherapy, consult your doctor to determine the most suitable option for your treatment plan.