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Biological response modifier as antigen: OK432-specific T-cell clone as an anti-tumor effector cell
1Department of Clinical Research, Utano National Hospital, Kyoto, Japan.
Abstract:
OK432, a Streptococcus preparation, is a biological response modifier that has been used in the treatment of malignant diseases. A cloned Thy 1.2+, L3T4+, Lyt 2.2- T cell (OK2.21), specific for OK432 and restricted to I-Ed, was isolated from BALB/c mice immunized with OK432. OK2.21 not only secreted interleukin 2 but also killed Iad-bearing B-lymphoma cells in an antigen-specific manner. The clone also killed Ia-negative bystander tumor targets, but only in the presence of both OK432 and antigen-presenting cells. Despite the cytotoxicity against tumor cells, OK2.21 did not kill OK432-pulsed normal spleen cells. Injection of this clone together with OK432 to tumor-bearing BALB/c mice prolonged their survival, suggesting that this clone acts as an anti-tumor effector (or effector-inducer) cell in the therapy with OK432.
Insights
This study identifies a specific T cell clone (OK2.21) that targets cancer cells when combined with OK432, a biological response modifier. This T cell therapy shows promise in prolonging survival for tumor-bearing mice.
Area of Science:
- Immunology
- Oncology
- Biotherapy
Background:
- OK432, a Streptococcus preparation, functions as a biological response modifier in treating malignant diseases.
- T cells play a crucial role in immune responses against cancer.
Purpose of the Study:
- To isolate and characterize a T cell clone specific for OK432.
- To evaluate the anti-tumor activity of the isolated T cell clone in vitro and in vivo.
Main Methods:
- Isolation of a cloned T cell (OK2.21) from BALB/c mice immunized with OK432.
- Assessment of interleukin 2 secretion and cytotoxicity against B-lymphoma cells and bystander tumor cells.
- In vivo studies involving the administration of the T cell clone and OK432 to tumor-bearing mice.
Main Results:
- The cloned T cell (OK2.21) demonstrated specificity for OK432 and I-Ed, secreting interleukin 2.
- OK2.21 exhibited antigen-specific cytotoxicity against Iad-bearing B-lymphoma cells.
- The clone also killed Ia-negative tumor cells in the presence of OK432 and antigen-presenting cells, but not normal spleen cells.
- Administration of OK2.21 with OK432 prolonged survival in tumor-bearing mice.
Conclusions:
- The identified T cell clone (OK2.21) possesses potent anti-tumor activity, both directly and potentially through effector induction.
- This T cell clone represents a promising candidate for enhancing OK432-based cancer immunotherapy.