Immunotherapy in Blood Cancers

Cancer immunotherapy is a rapidly evolving field of oncology that harnesses the power of the immune system to recognise, attack, and eradicate cancer cells. While conventional cancer treatments such as chemotherapy and radiation therapy have improved outcomes for many patients, these approaches often have significant limitations. In contrast, immunotherapies have shown the potential to achieve complete and durable responses in some patients, with the added benefit of constructing long-lasting immunity to prevent cancer recurrence.

The rationale behind cancer immunotherapy is that the immune system, when properly activated and directed, can mount a robust and persistent response against tumour cells. However, tumour cells have evolved various mechanisms to evade immune detection and suppress the anti-tumour immune response. Consequently, a major focus of cancer immunotherapy research has been on developing strategies to overcome these tumour-induced immune evasion and suppression mechanisms.

For leukaemia, lymphoma, and myeloma, several immunotherapy approaches have shown promise.

  1. Chimeric Antigen Receptor T-cell therapy (CAR T-cells)
    One prominent example is Chimeric Antigen Receptor T-cell therapy (CAR T-cells). This personalised treatment involves extracting a patient’s T cells (a type of immune cell) and genetically modifying them to express Chimeric Antigen Receptor. These receptors enable the CAR T-cells to recognise a specific proteins found on the surface of cancer cells, for example CD-19 on the cancerous lymphoma and leukaemia cells and thus initiate the T cell directed killing of the cancer cells. CAR T-cell therapy has demonstrated remarkable success in treating certain types of leukaemia and lymphoma, including B-cell acute lymphoblastic leukaemia and diffuse large B-cell lymphoma (i.e., Kymriah and Yescarta), myeloma (i.e., Abecma and Carvykti)

  1. Immune Checkpoint Inhibitors
    Cancer cells can evade immune detection, and immune checkpoint inhibitors are designed to counteract this. However, it’s not that these inhibitors directly detect and kill cancer cells. Instead, they work a bit more indirectly by cutting the brakes that cancer cells have put on the immune system.
    To explain, immune checkpoints are like brakes for our normal immune system to work. They prevent overactivation and autoimmune responses, which is crucial for a healthy immune system. Cancer cells exploit these checkpoints. They express proteins like PD-L1, which bind to PD-1 receptors on T-cells, effectively telling the T-cell, “Don’t attack me!” Immune checkpoint inhibitors release the brakes. Drugs like anti-PD-1 or anti-CTLA-4 antibodies block these inhibitory signals. This does not directly kill the cancer cell, but it allows the immune system to recognise it as a threat and mount an attackFor instance, inhibitors targeting PD-1/PD-L1 (e.g., Pembrolizumab, Nivolumab) and CTLA-4 have shown efficacy in treating various cancers, including lymphoma.

  1. Bispecific T-cell engagers (BiTEs)
    They are essentially engineered antibodies with two binding sites: one that latches onto a specific protein on cancer cells (e.g., CD19 by Blinatumomab in ALL, CD20 by Epcoritamab and Glofitamab in B-cell Lymphoma, BCMA by Teclistamab in multiple myeloma) and another that grabs onto a protein called CD3 found on T-cells.
    Think of BiTEs like a bridge connecting cancer cells and T-cells, forcing them into close proximity. This connection activates the T-cell, prompting it to release cytotoxic molecules that destroy the cancer cell.While BiTEs show great promise, they can also cause side effects such as cytokine release syndrome, which can be severe. There are medications that can potentially reduce the severity of these side effects such as steroids, anakinra, tocilizumab, siltuximab.

 

Article written by Dr Lee Chun Tsu, Consultant Haematologist, Centre for Clinical Haematology

Disclaimer:
The information on the Centre For Clinical Haematology website is intended for educational use.  It should not be considered or used as a substitute for medical advice, diagnosis or treatment from a qualified health professional.

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