Cancer Immunotherapy Requires New Approaches

With the recent development and commercialization of immunotherapy drugs such as checkpoint inhibitors, the field of immuno-oncology is transforming the treatment of cancer. However, cures remain elusive, and the majority of cancer patients experience only modest clinical benefit.

The challenge facing the field of immuno-oncology is to develop new approaches to drive potent and tumor-specific immune responses that provide therapeutic benefit to a large number of patients. The greatest successes in cancer immunotherapy to date have been driven by therapeutics that enhance tumor-specific T cells, an essential effector component of the immune system. 

 

Tumor-Specific Neoantigens: A New Class of Immune Targets

Gritstone’s founders helped discover that, in patients with solid tumors who respond clinically to checkpoint inhibitors, mutations in the tumor’s DNA produce critical new targets that are foreign to the immune system. These targets, called tumor-specific neoantigens, are typically unique to each patient’s tumor and are recognized and targeted for attack and destruction by the patient’s own killer T cells.

Neoantigens represent a new class of immune targets for advancing cancer immunotherapy and have been validated in cancer patients as critical T-cell targets. However, the identification of neoantigens presents a key therapeutic challenge. Tumors have hundreds of mutations that create candidate neoantigens, but only a minority result in true tumor-specific neoantigens – that is, antigens generated by DNA mutations within the tumor cell and presented as a T-cell target on the surface of the tumor cell.