Combined chemokine and cytokine gene transfer enhances antitumor immunity

Abstract

The probability of producing a specific antitumor response should be increased by multiplying the number of T lymphocytes that encounter the malignant cells. We tested this prediction in a murine model, using a recently discovered T-cell chemokine, lymphotactin (Lptn). This chemokine increased tumor cell infiltration with CD4+ lymphocytes but generated little antitumor activity. Coexpression of the T-cell growth factor interleukin-2, however, greatly expanded the T lymphocytes attracted by Lptn, affording protection from the growth of established tumor in a CD4+ and CD8+ T cell-dependent manner. Lesser synergy was seen with GM-CSF. Hence coexpression of a T-cell chemokine and T-cell growth factor potentiates antitumor responses in vivo, suggesting a general strategy to improve cancer immunotherapy.

Efficient antitumor immunity derived from maturation of dendritic cells that had phagocytosed apoptotic/necrotic tumor cells

“…inhibition of tumor growth and antitumor immune responses. 51,53,54 GM-CSF is a growth factor for hematopoietic progenitor cells. GM-CSF-secreting tumor cell vaccines have been shown to elicit tumoricidal antitumor immune responses by recruiting dendritic cells to immunization sites in animal models and in human clinical trials.…”

Macrophage-derived chemokine gene transfer results in tumor regression in murine lung carcinoma model through efficient induction of antitumor immunity

“…[30][31][32] MCP-1 was shown to reduce in vivo growth of tumor cells and to increase infiltration of macrophages/monocytes to the tumor site. 33 Recently, intratumoral injection of recombinant SLC showed potent antitumor response and led to tumor eradication in treated mice. 34 The expression of MIP-3␤/ELC(CK␤-11) in a breast cancer cell line mediated rejection of the transduced tumor.…”

Adenovirus-mediated lymphotactin gene transfer improves therapeutic efficacy of cytosine deaminase suicide gene therapy in established murine colon carcinoma

“…37 Cheon et al 16 reported that chemogene therapy could achieve better antitumor effects with reduced toxicity than the conventional chemotherapy or gene therapy protocols alone. They chose low-dose methotrexate to increase the chemosensitization of the tumor cells in combination with suicide gene therapy with an overall reduced toxicity and enhanced therapeutic efficacy.…”