Journal article
Identification of a T-Cell Receptor from a Therapeutic Murine T-Cell Clone
Journal of immunotherapy (1997), Vol.20(4), pp.247-255
07/1997
DOI: 10.1097/00002371-199707000-00001
PMID: 9220314
Abstract
Tumor-infiltrating lymphocytes (TIL) have been successfully used for the treatment of metastatic malignancies in clinical trials and in experimental animal models. Tumor-specific reactivity by TIL is mediated via receptors expressed on the surface of T cells (TcRs), which recognize tumor-associated antigens (TAA) presented in the context of MHC molecules on the surface of tumor cells. The current study was performed to identify the TcR a and P chains from a tumor-specific therapeutic TIL clone that can be used to develop a preclinical animal model for genetically modifying lymphocytes and hematopoietic progenitors with TcR genes. TIL 205 was generated from a subcutaneous implant of MCA-205 fibrosarcoma and at 21 days was cloned by limiting dilution. TIL clone 8, obtained from a culture seeded at one cell/well, mediated specific lysis and specific secretion of 7-interferon to MCA-205 and WP6, a subclone of MCA 205. No reactivity was observed against other syngeneic sarcoma lines. Anchor polymerase chain reaction analysis determined that antigen recognition by clone 8 was mediated by a TcR consisting of Va3/Ja27 and Vp8.2/Dp2.1/Dp2.4. Immunofluorescent staining with Vp subfamily specific monoclonal antibodies revealed that >95% of the T cells in TIL clone 8 expressed VP8.2, confirming that TIL clone 8 was indeed a clone. In contrast, -30% of the T cells in the parental TIL 205 expressed Vp8.2. The transfer of as few as 500,000 TIL clone 8 cells in conjunction with the systemic administration of recombinant human interleukin-2 mediated regression of established 3-day WP6 lung metastases. Thus, clone 8 recognizes a biologically relevant tumor rejection antigen, making the Va3/Ja27-Vp8.2/Dp2.1/jp2.4 TcR isolated from this clone useful as a probe for cloning the tumor-rejection antigen in the WP6 tumor as well as modeling, in mice, the TcR-based gene therapies being developed for humans
Details
- Title: Subtitle
- Identification of a T-Cell Receptor from a Therapeutic Murine T-Cell Clone
- Creators
- Joel Shilyansky - National Institutes of HealthJames C. Yang - National Institutes of HealthMary C. Custer - National Institutes of HealthPaul Spiess - National Institutes of HealthArnold Mixon - National Institutes of HealthDavid J. Cole - Medical University of South CarolinaJames J. Mul??Steven A. RosenbergMichael I. Nishimura - National Institutes of Health
- Resource Type
- Journal article
- Publication Details
- Journal of immunotherapy (1997), Vol.20(4), pp.247-255
- DOI
- 10.1097/00002371-199707000-00001
- PMID
- 9220314
- ISSN
- 1524-9557
- eISSN
- 1537-4513
- Language
- English
- Date published
- 07/1997
- Academic Unit
- Stead Family Department of Pediatrics; Surgery
- Record Identifier
- 9984322943502771
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