Cancer-Fighting T Cells Tuned To Viral Particles May Target Tumor Neoantigens

NEW YORK (GenomeWeb) – New research suggests cancer-fighting T-cells in the immune system may react more robustly to neoantigens formed from somatic or germline mutations in the tumors themselves than to antigens associated with particles from viruses such as human papillomavirus (HPV).

A National Cancer Institute-led research team used a combination of tandem minigene-borne antigens, assays, and T-cell receptor sequencing to profile overall T-cell responses in two individuals with HPV-positive, metastatic cervical cancer who had achieved lasting cancer regression after treatment with adoptive tumor-infiltrating lymphocyte transfer therapy.

“Our findings reveal a previously unrecognized participation of T-cells targeting non-viral tumor antigens in the immunotherapy of [HPV-positive] cervical cancer,” senior author Christian Hinrichs, an NCI experimental transplantation and immunology branch researcher, and his co-authors wrote.

Because T-cells that expressed the programmed death 1 (PD-1) protein were also those showing the most pronounced responses to the tumor and viral antigens after the adoptive cell therapy, they reasoned that adding in immunotherapy approaches that block the PD-1-based immune checkpoint may also “unleash diverse anti-tumor T-cell reactivities.”

For their analysis, reported today in Science, the researchers focused on two adoptive T-cell therapy-treated women with metastatic cervical cancer. The first patient had a form of HPV16+

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