HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Purification of L-selectin(low) cells promotes the generation of highly potent CD4 antitumor effector T lymphocytes.

Abstract
Successful adoptive immunotherapy of cancer requires the identification, isolation, and expansion of tumor-specific immune effector cells. A reliable source of tumor-immune lymphocytes is lymph nodes draining a growing tumor. After in vitro stimulation with anti-CD3 and expansion in IL-2, these cells are capable of mediating the regression of established tumors. In the absence of further Ag stimulation, we recently found that the down-regulation of the homing molecule L-selectin could serve as a surrogate marker for isolation of specific tumor-sensitized T cells. The L-selectin(low) (L-selectin-) T cells proliferated more vigorously than unfractionated or L-selectin(high) cells. In adoptive immunotherapy of established intracranial MCA 205 tumors, L-selectin- cells displayed at least 30-fold greater therapeutic efficacy than unfractionated cells. L-selectin(high) cells did not demonstrate any antitumor effects. Activated L-selectin- cells secreted a number of cytokines, including IFN-gamma, IL-2, IL-4, and IL-10, specifically when stimulated with cognate tumor cells. Further analysis revealed that CD4 T cells alone mediated tumor regression and secreted cytokines. Our results thus demonstrate that the purification of L-selectin- cells led to the generation of CD4 immune effector cells with unusually high therapeutic efficacy against chemically induced tumors. The lack of cytotoxicity and the ability to secrete cytokines suggest that these effector CD4 cells mediate antitumor effects through an indirect mechanism similar to the delayed hypersensitivity reaction.
AuthorsH Kagamu, S Shu
JournalJournal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 160 Issue 7 Pg. 3444-52 (Apr 01 1998) ISSN: 0022-1767 [Print] United States
PMID9531305 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Cytokines
  • L-Selectin
Topics
  • Animals
  • CD4-Positive T-Lymphocytes (immunology, metabolism, transplantation)
  • Cell Separation (methods)
  • Cells, Cultured
  • Cytokines (metabolism)
  • Cytotoxicity, Immunologic
  • Female
  • Fibrosarcoma (immunology, therapy)
  • Immunophenotyping
  • Immunotherapy, Adoptive (methods)
  • L-Selectin (analysis)
  • Lymph Nodes (immunology)
  • Lymphocyte Activation
  • Lymphocytes, Tumor-Infiltrating (immunology, transplantation)
  • Mice
  • Mice, Inbred C57BL
  • Sarcoma, Experimental (immunology, therapy)
  • Tumor Cells, Cultured

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: