Dr. William A. Haseltine is a distinguished scientist, philanthropist, author, and entrepreneur renowned for his pioneering work in genomics and regenerative medicine. A former Harvard Medical School professor, he has made many significant contributions to cancer and HIV/AIDS research.
Checkpoint inhibitors are a groundbreaking class of cancer treatment, but they come with two frustrating challenges. In some cases, tumors show no initial response, rendering the therapy ineffective from the outset. In others, tumors that respond early on can develop resistance, gradually undermining the treatment’s impact. Both scenarios leave doctors and researchers grappling with how to achieve durable control over cancer.
For some patients, checkpoint inhibitors can help reverse cancer’s clever tactic. The antibodies in these inhibitors bind to checkpoint proteins before cancer cells can; this overrides the cancer’s “stop” signal and restores the immune system's ability to identify and eliminate tumor cells.Resistance can show up in different ways. Some patients do not respond to the therapy at all—this is called primary resistance.
This is why T cell exhaustion is a significant hurdle in overcoming resistance. Constant exposure to the unfriendly and immunosuppressive environment around the tumor impairs white blood T cells and forces them into an exhausted, dysfunctional state. When this happens, the T cells express additional immune checkpoints that slow their activity, and they become less efficient at recognizing and eliminating cancer cells.
What if one treatment could do the work of two inhibitors? That’s the goal of bispecific antibodies, which target two immune checkpoints at once. One-targeting antibodies can elicit a response in patients whose cancer has progressed after taking PD-1 targeting therapies. Still, heightened immune system activation from either therapy carries a trade-off: a higher risk of immune-related side effects.
Treatment Resistance Tumor Resistance Immune Checkpoints PD-1 Chemotherapy Cancer Melanoma Personalized Medicine CAR T Therapy
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