Faculty Collaboration Database

Immune responsiveness to a murine mammary carcinoma modified to express B7-1, interleukin-12, or GM-CSF. Cancer Gene Ther 1997;4(3):157-66

Date

05/01/1997

Pubmed ID

9171934

Scopus ID

2-s2.0-0031137564 (requires institutional sign-in at Scopus site)   28 Citations

Abstract

This report characterizes the immunological host response to a syngeneic murine mammary carcinoma along with variants genetically modified to express B7-1 or secrete GM-CSF and interleukin-12 (IL-12). MT-901 is a subline of a mammary adenocarcinoma that was chemically induced in the Balb/c host. It was found to be weakly immunogenic by immunization/ challenge experiments, and it induced tumor-specific T-cell responses in lymph nodes (LN) draining progressive subcutaneous tumors. Tumor clones expressing B7-1 or secreting GM-CSF exhibited reduced tumorigenicity without completely abrogating tumor growth, whereas IL-12 elaboration lead to complete tumor growth inhibition. In vivo subcutaneous inoculation of a transgenic cell clone secreting GM-CSF (240 ng/10(6) cells/24 hours) resulted in significantly enhanced T-cell reactivity of tumor-draining lymph node (TDLN) cells as compared to wild-type TDLN cells. This finding was obtained from observations assessed by several different methods, including: 1) in vitro cytotoxicity, 2) in vitro interferon-gamma release, and 3) adoptive transfer in mice with established tumor. Moreover, the transfer of activated LN cells derived from mice inoculated with GM-CSF-secreting tumor cells resulted in the prolonged survival of animals with macroscopic metastatic disease, which was not evident utilizing LN cells from mice inoculated with wild-type tumor. By contrast, clones that expressed B7-1 or IL-12 (4 ng/10(6) cells/24 hours) did not elicit enhanced tumor-reactive TDLN cells compared with wild-type tumor when assessed in the adoptive transfer model. The autocrine secretion of GM-CSF by transduced tumor cells was found to serve as an effective immune adjuvant in the host response to this weakly immunogenic tumor.

Author List

Aruga E, Aruga A, Arca MJ, Lee WM, Yang NS, Smith JW 2nd, Chang AE

MESH terms used to index this publication - Major topics in bold

Adenocarcinoma
Animals
B7-1 Antigen
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Female
Granulocyte-Macrophage Colony-Stimulating Factor
Immunotherapy, Adoptive
Interleukin-12
Lung Neoplasms
Lymph Nodes
Lymphocyte Depletion
Mammary Neoplasms, Experimental
Mice
Mice, Inbred BALB C
Neoplasm Transplantation
T-Lymphocyte Subsets
Transfection
Tumor Cells, Cultured