Types of Cancer Immunotherapy and Their Mechanisms

Cancer immunotherapy uses or modifies immune responses to recognise and attack cancer cells. Its approaches range from releasing inhibitory signals on immune cells to engineering cells or using antibodies, viruses and vaccines to strengthen tumour-directed immunity.

Immune Surveillance and Cancer Evasion

The immune system protects the body from pathogens and abnormal cells. T cells can distinguish healthy from unhealthy cells, but cancers may evade this surveillance by exploiting inhibitory checkpoints or by lacking antigens that immune cells can recognise. Immunotherapy seeks to overcome these escape mechanisms and promote an anti-tumour response. Immune regulation is central to this approach: therapies must enable effective tumour control while working through the body’s immune defences. The methods differ in how they identify cancer and activate or direct immune activity.

• Immune checkpoints: These are inhibitory signals that can restrain T-cell activity. Tumours may exploit them to reduce the likelihood of an immune attack.
• Tumour antigens: These are targets that immune cells or therapies can recognise on cancer cells. Some approaches rely on existing antigens; others engineer immune cells to recognise a selected target.

Immune Checkpoint Inhibitors

Immune checkpoint inhibitors (ICIs) block inhibitory proteins on immune cells or cancer cells. By removing these “brakes”, they can help T cells mount a stronger anti-tumour response. Two key targets are PD-1/PD-L1 and CTLA-4.

• PD-1/PD-L1 pathway: Programmed cell death protein 1 (PD-1) is a checkpoint receptor on T cells. Cancer cells may express programmed death-ligand 1 (PD-L1), which binds to PD-1 and sends an inhibitory signal. PD-1 inhibitors block the receptor; PD-L1 inhibitors block the ligand.
• CTLA-4 pathway: Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is an inhibitory receptor on T cells. Blocking it can increase T-cell activation and proliferation, strengthening the anti-tumour response.
• Precision medicine: Checkpoint therapies target defined immune pathways. In some treatment settings, patient selection may consider tumour markers; requirements can vary by indication and regulatory approval.

Checkpoint inhibitors do not directly remove every cancer cell. Instead, they alter immune signalling so that T cells can better recognise or attack tumours. This makes immune regulation an important consideration: the aim is to release inhibitory signals while maintaining appropriate control of immune activity.

CAR T-Cell Therapy and Monoclonal Antibodies

Chimeric antigen receptor (CAR) T-cell therapy modifies a patient’s own T cells so they can recognise a selected cancer-cell antigen. It is a specialised, individualised treatment process.

1. Collection: T cells are taken from the patient’s blood through apheresis.
2. Engineering: The cells are genetically modified in a laboratory to express a CAR, a synthetic receptor designed to recognise an antigen on cancer cells.
3. Expansion and infusion: The modified cells are multiplied and infused back into the patient.
4. Targeted action: CAR T cells bind to cancer cells carrying the target antigen and can destroy them. The therapy has shown significant success in certain blood cancers.

Monoclonal antibodies (mAbs) are laboratory-produced proteins that mimic natural antibodies. Non-checkpoint mAbs can act in several ways:

• Direct targeting: Binding to cancer-cell antigens can block growth signals or induce programmed cell death, also called apoptosis.
• Immune flagging: Antibodies can mark cancer cells, making them more visible to other immune cells.
• Drug delivery: Antibody-drug conjugates (ADCs) link an antibody to a chemotherapy drug, directing the drug towards cancer cells and aiming to limit harm to healthy tissues.

Oncolytic Viruses and Cancer Vaccines

Oncolytic viruses are naturally occurring or genetically engineered viruses intended to infect and kill cancer cells selectively, while sparing healthy cells. They can also stimulate a wider immune response.

• Direct lysis: Viruses replicate inside cancer cells, causing them to burst and die; this process is called oncolysis.
• Immune stimulation: Cell lysis releases tumour-associated antigens and danger signals that can alert and activate the immune system.

Cancer vaccines either help prevent cancers caused by particular viruses or stimulate immunity against existing tumours.

• Preventive vaccines: HPV vaccination helps prevent infection with a virus associated with cervical cancer; hepatitis B vaccination helps prevent infection associated with liver cancer.
• Therapeutic vaccines: These aim to train the immune system to target tumour antigens and may help prevent recurrence. Examples include sipuleucel-T for prostate cancer and BCG for bladder cancer.

These approaches illustrate how biomedical innovation can direct or strengthen immune responses. Access to complex treatments, including engineered-cell therapies, is also a precision-medicine consideration.

Key Prelims Takeaways

• ICIs: Block immune checkpoints, including PD-1, PD-L1 and CTLA-4, to release inhibitory signals on immune responses.
• CAR T-cell therapy: Uses a patient’s genetically modified T cells to target a specific cancer-cell antigen.
• Monoclonal antibodies: Can target cancer cells directly, flag them for immune destruction or deliver a drug through an ADC.
• Oncolytic viruses: Kill cancer cells through oncolysis and may stimulate anti-tumour immunity.
• Cancer vaccines: May be preventive, such as HPV and hepatitis B vaccines, or therapeutic, such as sipuleucel-T and BCG.
• Regulation in India: CDSCO is the national regulator for drugs, medical devices and cosmetics. The DCGI leads it and performs regulatory duties under the Drugs and Cosmetics Act, 1940, which remains in force and has been amended. Dr. Rajeev Singh Raghuvanshi is the current DCGI.
• International context: Dr. Reddy’s Laboratories and Junshi Biosciences made a licensing and commercialisation agreement for toripalimab across 21 countries in 2023. The US FDA approved it as Loqtorzi for nasopharyngeal carcinoma on October 27, 2023; the EMA approved it for nasopharyngeal carcinoma and ESCC on September 25, 2024. The UK MHRA approved it on November 16–18, 2024, for recurrent or metastatic nasopharyngeal carcinoma and first-line ESCC treatment. EMA and MHRA ESCC approvals apply irrespective of PD-L1 expression.

Recent Context

On October 21, 2026, DCGI approved Zytorvi (toripalimab) with cisplatin and paclitaxel as first-line treatment for unresectable advanced, recurrent or metastatic ESCC, its second Indian indication after nasopharyngeal carcinoma. JUPITER-06 showed 42% lower progression-or-death risk; median overall survival was 17.7 versus 12.9 months. PD-L1 selection is not required.