Three-Dimensional System to Measure Lymphocyte Migration

Inventors: Dorothee Herlyn, Meenhard Herlyn, Rajasekharan Somasundaram

Tech ID: HD01002

Description: There is a need for model systems that can be used to identify clinically relevant behaviors of cytotoxic T lymphocytes (CTL), including tumor cell lysis and active migration, as well as systems that can be used to identify chemokines and tumor antigens that influence active migration of CTL towards tumor cells. Traditionally, CTL are raised and studied in two-dimensional mixed lymphocyte tumor cell culture (MLTC) that includes either (1) long-term cultured tumor cells to stimulate peripheral blood mononuclear cells (PBMC) for CTL induction or (2) disaggregated tumor tissue with tumor infiltrating lymphocytes (TIL) where both types of cultures are two dimensional and are grown directly on plastic surfaces. Studies in melanoma and colon cancer patients have shown that characterization of CTL responses using such two-dimensional cultures do not reflect the CTL’s in vivo behavior and specifically, CTL-exerted anti-tumoral activity.

Wistar scientists have developed a three-dimensional reconstruct model containing solid layers of collagen, tumor cells and CTL that closely mimic the condition of patients in vivo, preserving in vivo semi-phenotypic and functional characteristics of the cells. This model closely mimics CTL behavior in cancer patients and allows the detection of CTL migration and identification of tumor antigens and cytokines/chemokines involved in CTL migration.

Key Words: cytotoxic T lymphocyte, CTL, tumor antigen, chemokine, cytokine, cancer immunotherapy

Applications and Advantages: The technology is a new method for: (1) detecting and measuring active and clinically-relevant migration of CTL towards tumor cells; (2) characterization of migrating CTL phenotype and function; (3) In vitro identification of chemokines and cytokines that affect active migration of CTL towards cancer cells; and (4) cloning of relevant tumor antigens that are recognized by migrating CTL. This technology may be useful for the development of systems or kits to measure responses of CTL to various stimuli such as tumor antigens and cytokines.

Intellectual Property Status: This technology is protected by U.S. patent no. 7,544,465, “Methods & Compositions for Monitoring Cell Migration and Identifying Clinically Relevant Cytotoxic T-Lymphocyte Activity” issued June 09, 2009.

Licensing Opportunity: This technology is available for exclusive or non-exclusive license. 

Relevant Publication: 
Zhang T, Somasundaram R, Berking C, Caputo L, Van Belle P, Elder D, Czerniecki B, Hotz S, Schuchter L, Spitz FR, Berencsi K, Rani P, Marincola F, Qiu R, Herlyn D. (2006) “Preferential involvement of CX chemokine receptor 4 and CX chemokine ligand 12 in T-cell migration toward melanoma cells.” Cancer Biol Ther. 5(10):1304-1312.

Berencsi K, Meropol NJ, Hoffman JP, Sigurdson E, Giles L, Rani P, Somasundaram R, Zhang T, Kalabis J, Caputo L, Furth E, Swoboda R, Marincola F, Herlyn D. (2007) “Colon carcinoma cells induce CXCL11-dependent migration of CXCR3-expressing cytotoxic T lymphocytes in organotypic culture.” Cancer Immunol Immunother. 56(3):359-370.

Zhang T, Somasundaram R, Berencsi K, Caputo L, Gimotty P, Rani P, Guerry D, Swoboda R, Herlyn D.  (2006) “Migration of cytotoxic T lymphocytes toward melanoma cells in three-dimensional organotypic culture is dependent on CCL2 and CCR4.” Eur J Immunol. 36(2):457-467.

Zhang T, Somasundaram R, Berencsi K, Caputo L, Rani P, Guerry D, Furth E, Rollins BJ, Putt M, Gimotty P, Swoboda R, Herlyn M, Herlyn D. (2005) “CXC chemokine ligand 12 (stromal cell-derived factor 1 alpha) and CXCR4-dependent migration of CTLs toward melanoma cells in organotypic culture.” J Immunol. 174(9):5856-5863.

Contact:

George G. Pipia, Ph.D.
Associate Director, Business Development
The Wistar Institute
Phone:  (215) 495-6855
gpipia@wistar.org

Last updated: May-09