Clinical experience in phase I and phase II testing of direct intratumoral administration with allovectin-7: a gene-based immunotherapeutic agent (Meeting abstract).

Important note: Information in this article was accurate in 1997. The state of the art may have changed since the publication date.

Clinical experience in phase I and phase II testing of direct intratumoral administration with allovectin-7: a gene-based immunotherapeutic agent (Meeting abstract).

Proc Annu Meet Am Soc Clin Oncol; 15:A578 1996. Unique Identifier : AIDSLINE ICDB/97635578
Vogelzang NJ; Sudakoff G; Hersh EM; Stopeck A; Rubin J; Galanis E; Schreiber A; Stahl S; University of Chicago, Medical Center, Chicago, IL 60637

Abstract: We have completed 3 phase I studies to determine the safety of direct intratumoral injection of allovectin-7, an allogeneic MHC class I gene, HLA-B7, in a DNA plasmid formulated with a cationic lipid in 47 (43 evaluable) HLAB7 negative patients (pts) with advanced metastatic melanoma (MM; n=14), colorectal cancer (CC; n=15) and renal cell carcinoma (RCC; n=14). Groups of 3 pts per tumor type were to be treated with 10, 50, or 250 ug of allovectin-7 given once; 10 ug given twice or 10 ug given 3 times at 2 week intervals. Tumor biopsies were analyzed for evidence of gene uptake, HLA-B7 protein expression and immunohistochemistry (IHC). Adverse reactions were generally limited to mechanical effects of tumor injection. There was evidence of gene uptake by PCR and HLA-B7 expression by IHC or FACS in 98% of the pts; CD8+ T cell infiltration was observed in 22 of 23 available samples and anti-HLA CTLs were found in the peripheral blood of 23 of 43 post-gene therapy samples. No significant tumor shrinkage was observed in pts with RCC or CC and the median survival time (MST) was 8 months. In pts with MM, 7 of 14 showed shrinkage of the injected nodule (range 28-87% of the product of 2 diameters). Transient shrinkage of non-injected nodules was also observed. One pt with a single retrocaval mass had a complete response. A multicenter phase II 2 stage trial using a multiple dosing regimen in pts with relatively lower tumor burden was initiated in September of 1995 and will enter MM, RCC, CC as well as pts with metastatic breast carcinoma and non-Hodgkin's lymphoma. A total accrual of 25 pts per disease is planned if responses are seen in the first 19 pts. Seven pts have entered as of 11/95; 4 MM, 2 CC and 1 lymphoma.

Keywords: CD8-Positive T-Lymphocytes/IMMUNOLOGY Carcinoma, Renal Cell/IMMUNOLOGY/*THERAPY Colorectal Neoplasms/IMMUNOLOGY/*THERAPY *Gene Transfer HLA-B7 Antigen/GENETICS Human *Immunotherapy Kidney Neoplasms/IMMUNOLOGY/*THERAPY Lipids/*THERAPEUTIC USE Melanoma/IMMUNOLOGY/*THERAPY Neoplasm Metastasis Plasmids/*THERAPEUTIC USE T-Lymphocytes, Cytotoxic/IMMUNOLOGY beta 2-Microglobulin/GENETICS ABSTRACT CLINICAL TRIAL
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