NCT04180774

Safety and Efficacy of Tag-7 Gene-modified Vaccine in Locally Advanced or Metastatic Malignant Melanoma or Kidney Cancer

An Open-label Study of the Safety and Efficacy of Tag-7 Gene-modified Tumor Cell-based Vaccine in Patients With Locally Advanced or Metastatic Malignant Melanoma or Renal Cell Cancer

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 80 (actual)
• Sponsor: N.N. Petrov National Medical Research Center of Oncology · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study was designed to assess the safety and efficacy of inactivated tumor cells genetically modified with the TAG-7 gene as immunotherapy for cancer. Patients with melanoma or kidney cancer were included since they have immune-dependent tumors. Treatment was done in the adjuvant setting after complete cytoreduction of locally advanced or metastatic disease or in the therapeutic setting in patients where complete cytoreduction was impossible.

Detailed description

During the last decade, novel approaches for cancer treatment have been developed. Antitumor vaccines are one of the most promising approaches in tumor immunotherapy. Tumor cells possess low immunogenicity properties due to a number of the not completely understood mechanisms of resistance. One of the ways to overcome it is immune genes transfection. Genes encoding granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-2 and IL-12 have been used most commonly, both in preclinical studies and clinical trials. These cytokines are well known to participate in the systemic immune response. Several studies have shown that the professional antigen-presenting cells (APCs) of the host, rather than the vaccinating tumor cells themselves, are responsible for priming CD4+ and CD8+ T cells, both of which are required to generate systemic antitumor immunity. Recent findings indicate that the adaptive arm of immunity is governed by the innate immune mechanisms that control the co-stimulatory signaling of APCs. Recently, investigators identified a novel gene, tag7, also know as PGRP-S. The insect ortholog of the tag7/PGRP-S was shown to be involved in the innate immune response in Drosophila. In preclinical studies, tag7-modified mouse tumor cells induced a long-lasting T-cell dependent immune response in mice. The effectiveness of antitumor vaccination was demonstrated on different models of mouse tumors, particularly for melanoma cells (M3, B16, F10). Clinically important results of vaccine therapy were achieved in patients with melanoma and renal carcinoma in a number of studies. The results with this treatment are comparable to chemotherapy and immunotherapy. Investigators assume that one has to activate the innate component of immunity first, followed by the activation of the adaptive one, to make anticancer vaccines more effective. Thus, a phase I/II clinical trial has been performed to evaluate the feasibility and toxicity of treatment with autologous tumor cells modified with the tag7 gene, which has been shown to be involved in innate immunity mechanisms,

Conditions

• Melanoma
• Kidney Cancer

Interventions

Type	Name	Description
BIOLOGICAL	Tag-7 gene modified inactivated tumor cells	Patients received GMV once in three weeks subcutaneously in three points in the paravertebral region. One dose consisted of 10 million transfected and inactivated tumor cells. No dose reduction was allowed.

Timeline

• Start date: 2001-01-31
• Primary completion: 2018-12-31
• Completion: 2018-12-31
• First posted: 2019-11-29
• Last updated: 2019-12-06

Locations

1 site across 1 country: Russia