Complete elimination ('cure') of progressively growing intraocular tumors by local injection of tumor-specific CD8+ T lymphocytes.
OBJECTIVE
The purpose of this study was to examine if anterior chamber tumors could be eliminated by adoptive immunotherapy.


METHODS
Precursor T cells were recovered from lymph nodes draining subconjunctival space or anterior chamber tumors and restimulated in vitro to obtain fully functional tumor-specific CD8+ cytolytic T cells.


RESULTS
Subconjunctival space tumor-derived cytolytic T cells eliminated tumors completely when injected simultaneously into the eye with the tumor cells, or when the anterior chamber injection was delayed for up to 3 days. In vitro restimulated cytolytic T cells obtained from lymph nodes draining progressively growing anterior chamber tumors were as effective as those obtained from lymph nodes draining subconjunctival space tumors, indicating that mice with anterior chamber tumors possess precursor cytotoxic T cells with the potential to differentiate into cytolytic T cells capable of eliminating intraocular tumors. By determining the frequency of tumor-specific cytolytic T cells in the effector cell inocula, it was estimated that cures of intraocular tumors are possible when the ratio of cytolytic T cells to tumor cells is less than 1:50, and the total tumor burden at the time of adoptive immunotherapy is less than 80,000 viable tumor cells.


CONCLUSIONS
It was concluded that terminally differentiated, antigen-specific, cytotoxic T cells injected directly into an intraocular tumor site are capable of eliminating the tumor, and may represent a mode of ocular tumor immunotherapy in the future.
Miki
S
S
Department of Microbiology and Immunology, University of Miami Medical School, Florida 33101.
Ksander
B
B
Streilein
J W
JW
D000818:Animals; D000867:Anterior Chamber; D005134:Eye Neoplasms / Q000473:pathology / Q000628:therapy*; D005260:Female; D016219:Immunotherapy, Adoptive; D015552:Injections, Intralesional; D008213:Lymphocyte Activation; D016246:Lymphocytes, Tumor-Infiltrating; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D016513:Mice, SCID; D013602:T-Lymphocytes, Cytotoxic; D050378:T-Lymphocytes, Regulatory; D014407:Tumor Cells, Cultured