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Human c-erbB-2 proto-oncogene product as a target for bispecific-antibody-directed adoptive tumor immunotherapy
T Nishimura1, Y Nakamura, H Tsukamoto
1Department of Immunology, Tokai University School of Medicine, Isehara, Japan.
Abstract:
To develop an efficient strategy for the targeting of anti-tumor effector cells, we prepared bispecific antibody (BsAb) containing anti-CD3 and an anti-c-erbB-2 proto-oncogene product. The prepared BsAb specifically reacts with both c-erbB-2-positive tumor cells and CD3+ CTL. Human CD4+ helper/killer T cells, induced from peripheral-blood mononuclear cells by activation with immobilized anti-CD3 monoclonal antibody (MAb) plus IL-2, showed no significant cytotoxicity against tumor cells. However, treatment of human CD4+ helper/killer cells with the BsAb caused the induction of specific cytotoxicity against c-erbB-2-positive tumor cells. CD4+ helper/killer cells also produced significant amounts of IL-2 during co-culture with c-erbB-2-positive tumor cells in the presence of the BsAb. Moreover, by combination with the BsAb, CD4+ helper/killer cells showed a strong in vivo anti-tumor effect against c-erbB-2 transfectant or human colon-cancer cells implanted in nude mice. Our results strongly suggest that the c-erbB-2 proto-oncogene product on human tumor cells may be a good target for BsAb-directed adoptive tumor immunotherapy.
Insights
This study developed a bispecific antibody (BsAb) to target anti-tumor effector cells. The BsAb successfully induced specific anti-tumor activity in CD4+ T cells against c-erbB-2-positive tumor cells.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- Developing effective strategies for targeting anti-tumor effector cells is crucial in cancer immunotherapy.
- The c-erbB-2 proto-oncogene product is present on certain human tumor cells, making it a potential therapeutic target.
Purpose of the Study:
- To create an efficient bispecific antibody (BsAb) strategy for targeting anti-tumor effector cells.
- To evaluate the efficacy of a BsAb targeting both CD3+ T cells and the c-erbB-2 proto-oncogene product on tumor cells.
Main Methods:
- Preparation of a bispecific antibody (BsAb) with specificity for CD3 and c-erbB-2.
- Induction of human CD4+ helper/killer T cells from peripheral blood mononuclear cells.
- Assessment of T cell cytotoxicity against c-erbB-2-positive tumor cells in vitro and in vivo.
Main Results:
- The prepared BsAb specifically recognized both c-erbB-2-positive tumor cells and CD3+ T cells.
- BsAb treatment induced specific cytotoxicity in CD4+ helper/killer T cells against c-erbB-2-positive tumor cells.
- In vivo studies demonstrated a strong anti-tumor effect of BsAb-treated T cells against implanted human tumor cells in nude mice.
Conclusions:
- Bispecific antibody-directed adoptive immunotherapy targeting the c-erbB-2 proto-oncogene product shows significant potential.
- CD4+ helper/killer T cells can be effectively redirected to kill tumor cells using BsAb technology.
- The c-erbB-2 proto-oncogene product represents a viable target for BsAb-based cancer immunotherapy.