1. CD8(+) T Cells Impact Rising PSA in Biochemically Relapsed Cancer Patients Using Immunotherapy Targeting Tumor-Associated Antigens
- Author
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Elizabeth I. Heath, Young E. Whang, David B. Weiner, Li Liu, Scott T. Tagawa, Ronald Tutrone, Kimberly A. Kraynyak, Matthew P. Morrow, Mark L. Bagarazzi, Jean D. Boyer, Jocelyn Cheung, Trevor McMullan, Neal D. Shore, Heather H. Cheng, Samantha Rosencranz, W. Kevin Kelly, Jorge A. Garcia, Leonard Joseph Appleman, Brian Sacchetta, Jeffrey M. Skolnik, Albert Sylvester, Khamal Bhatt, and Luke T. Nordquist
- Subjects
Oncology ,Biochemical recurrence ,Glutamate Carboxypeptidase II ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Androgen deprivation therapy ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Antigen ,Internal medicine ,Drug Discovery ,Genetics ,medicine ,Cytotoxic T cell ,Humans ,Molecular Biology ,030304 developmental biology ,Aged ,Pharmacology ,Aged, 80 and over ,0303 health sciences ,business.industry ,Immunogenicity ,Immunity ,Prostatic Neoplasms ,Immunotherapy ,Genetic Therapy ,Middle Aged ,Prostate-Specific Antigen ,medicine.disease ,Interleukin-12 ,Progression-Free Survival ,Radiation therapy ,030220 oncology & carcinogenesis ,Antigens, Surface ,Molecular Medicine ,Original Article ,Neoplasm Recurrence, Local ,business ,Follow-Up Studies ,Plasmids ,T-Lymphocytes, Cytotoxic - Abstract
The management of men with prostate cancer (PCa) with biochemical recurrence following local definitive therapy remains controversial. Early use of androgen deprivation therapy (ADT) leads to significant side effects. Developing an alternative, clinically effective, and well-tolerated therapy remains an unmet clinical need. INO-5150 is a synthetic DNA therapy that includes plasmids encoding for prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA), and INO-9012 is a synthetic DNA plasmid encoding for interleukin-12 (IL-12). This phase 1/2, open-label, multi-center study enrolled men with PCa with rising PSA after surgery and/or radiation therapy. Patients were enrolled into one of four treatment arms: arm A, 2 mg of INO-5150; arm B, 8.5 mg of INO-5150; arm C, 2 mg of INO-5150 + 1 mg of INO-9012; and arm D, 8.5 mg of INO-5150 + 1 mg of INO-9012. Patients received study drug with electroporation on day 0 and on weeks 3, 12, and 24, and they were followed for up to 72 weeks. Sixty-two patients were enrolled. Treatment was well tolerated. 81% (50/62) of patients completed all visits. 85% (53/62) remained progression-free at 72 weeks. PSA doubling time (PSADT) was increased when assessed in patients with day 0 PSADT ≤12 months. Immunogenicity was observed in 76% (47/62) of patients by multiple assessments. Analysis indicated that CD38 and perforin co-positive CD8 T cell frequency correlated with attenuated PSA rise (p = 0.05, n = 50).
- Published
- 2020