Intratumoral Plasmid IL12 Electroporation Therapy in Patients with Advanced Melanoma Induces Systemic and Intratumoral T-cell Responses

Autor: Christopher G. Twitty, Lawrence Fong, Mai H. Le, Alan Paciorek, Kathryn Toshimi Takamura, Alain Algazi, Lawrence Chen, Katy K. Tsai, Samantha K. Greaney, Li Zhang, Robert H. Pierce, Adil Daud
Rok vydání: 2020
Předmět:
0301 basic medicine
Cancer Research
Skin Neoplasms
T cell
Population
Clinical Trials and Supportive Activities
Immunology
Oncology and Carcinogenesis
CD8-Positive T-Lymphocytes
03 medical and health sciences
Interferon-gamma
0302 clinical medicine
Immune system
Antigen
Immunologic
Clinical Research
medicine
Tumor Microenvironment
Humans
Adjuvants
Antigens
education
Melanoma
Neoplasm Staging
Cancer
Tumor microenvironment
education.field_of_study
business.industry
ELISPOT
Inflammatory and immune system
Immunity
Pharmacology and Pharmaceutical Sciences
Interleukin-12
030104 developmental biology
medicine.anatomical_structure
Treatment Outcome
Electroporation
030220 oncology & carcinogenesis
Cancer research
Interleukin 12
Neoplasm
Immunotherapy
Cellular
Patient Safety
business
CD8
Biomarkers
Plasmids
Zdroj: Cancer immunology research, vol 8, iss 2
Popis: Whereas systemic IL12 is associated with potentially life-threatening toxicity, intratumoral delivery of IL12 through tavokinogene telseplasmid electroporation (tavo) is safe and can induce tumor regression at distant sites. The mechanism by which these responses are mediated is unknown but is presumed to result from a cellular immune response. In a phase II clinical trial of tavo (NCT01502293), samples from 29 patients with cutaneous melanoma with in-transit disease were assessed for immune responses induced with this treatment. Within the blood circulating immune cell population, we found that the frequencies of circulating PD-1+ CD4+ and CD8+ T cells declined with treatment. Circulating immune responses to gp100 were also detected following treatment as measured by IFNγ ELISpot. Patients with a greater antigen-specific circulating immune response also had higher numbers of CD8+ T cells within the tumor. Clinical response was also associated with increased intratumoral CD3+ T cells. Finally, intratumoral T-cell clonality and convergence were increased after treatment, indicating a focusing of the T-cell receptor repertoire. These results indicated that local treatment with tavo can induce a systemic T-cell response and recruit T cells to the tumor microenvironment.
Databáze: OpenAIRE
Externí odkaz: