Your Donations in Action: Angela Jia, MD, PhD
Pilot study of radiopharmaceutical for treatment of HPV
Human papillomavirus (HPV) causes squamous cell cancers (SqCC) of the oropharynx, uterine cervix, anus, vulva and vagina. HPV-associated SqCC are highly radiosensitive but there are limited systemic treatment options to address metastatic disease.
HPV-associated viral oncoprotein E7 is an attractive therapeutic target because of its constitutive, or ongoing, expression in malignant cells and its absence in normal tissue. The challenge in targeting E7 has been its intracellular location.
Recently, an E7-specific human HLA-A*02:01 T-cell receptor (TRC) was identified in the setting of T-cell immunotherapy. To date, there have been no radiopharmaceuticals successfully targeting HPV-associated SqCC nor the use of radiolabeled TCRs to target intracellular cancer-specific antigens.
For her 2020 RSNA Research Resident grant project, “A Pilot Study of HPV E7-specific Soluble T-cell Receptor Radiopharmaceutical Therapy,” Angela Jia, MD, PhD, assistant professor of radiation oncology and director of genitourinary radiation oncology at the Seidman Cancer Center at Case Western Reserve University in Cleveland, and colleagues sought to design and test a soluble version of the E7-specific TCR (not connected to the T-cell), radiolabeled for radiopharmaceutical therapy.
The team successfully generated a soluble E7-specific, HLA-A*02:01-restricted TCR that maintains authentic binding to HLA-E7. “Our preliminary data generates rationale for clinical development of E7-sTCR-RPT for HPV-related cancers and using soluble TCR-RPTs as a novel platform to target other intracellular cancer specific antigens,” Dr. Jia said.
Funding from the R&E Foundation grant helped Dr. Jia amplify the scope and impact of her research. “The R&E grant was critical in my career development, as it afforded me the opportunity to conduct basic science research and generate preliminary data for NIH Trailblazer Awards,” Dr. Jia said.
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Read our previous Your Donations in Action article.