CD8(+) T Cells Impact Rising PSA in Biochemically Relapsed Cancer Patients Using Immunotherapy Targeting Tumor-Associated Antigens
| Autor: | 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, Luke T. Nordquist |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
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 |
| Zdroj: | Mol Ther |
| Popis: | 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). |
| Databáze: | OpenAIRE |
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