Cell retargeting by bispecific monoclonal antibodies. Evidence of bypass of intratumor susceptibility to cell lysis in human melanoma.

P Nisticò; R Mortarini; L B De Monte; A Mazzocchi; M Mariani; F Malavasi; G Parmiani; P G Natali; A Anichini

doi:10.1172/JCI115925

Laboratorio di Immunologia, Istituto Tumori Regina Elena, Rome, Italy.

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Laboratorio di Immunologia, Istituto Tumori Regina Elena, Rome, Italy.

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Laboratorio di Immunologia, Istituto Tumori Regina Elena, Rome, Italy.

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Laboratorio di Immunologia, Istituto Tumori Regina Elena, Rome, Italy.

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Laboratorio di Immunologia, Istituto Tumori Regina Elena, Rome, Italy.

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Laboratorio di Immunologia, Istituto Tumori Regina Elena, Rome, Italy.

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Laboratorio di Immunologia, Istituto Tumori Regina Elena, Rome, Italy.

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Laboratorio di Immunologia, Istituto Tumori Regina Elena, Rome, Italy.

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Laboratorio di Immunologia, Istituto Tumori Regina Elena, Rome, Italy.

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Published in Volume 90, Issue 3 on September 1, 1992
J Clin Invest. 1992;90(3):1093–1099. https://doi.org/10.1172/JCI115925.
© 1992 The American Society for Clinical Investigation

Published September 1, 1992 - Version history

Intratumor heterogeneity for susceptibility to cytotoxic T lymphocytes (CTL)-mediated lysis represents a major obstacle to cancer adoptive immunotherapy. To overcome the heterogeneity observed in terms of susceptibility of target cells to cell-mediated lysis, in this study we used two purified bispecific monoclonal antibodies (bsmAbs) that recognize molecules expressed by cytotoxic effector cells (CD3 and IgG Fc receptorial molecules), as well as one high molecular weight melanoma-associated antigen (HMW-MAA). The ability of these reagents to enhance or induce a relevant in vitro cytotoxic activity by a CTL clone (CTL 49) isolated from PBL of a melanoma patient was tested on a large panel of autologous and allogeneic melanoma cell lines and clones. Functional studies revealed that the CTL 49 clone lysed all the HMW-MAA+ tumor lines in the presence of bsmAbs and that these reagents affected the target lysis in a cooperative fashion. The effectiveness of bsmAbs in overcoming the heterogeneous susceptibility of human melanoma cells to cell-mediated lysis may find practical implications in cancer adoptive immunotherapy.

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Cell retargeting by bispecific monoclonal antibodies. Evidence of bypass of intratumor susceptibility to cell lysis in human melanoma.

P Nisticò, R Mortarini, L B De Monte, A Mazzocchi, M Mariani, F Malavasi, G Parmiani, P G Natali, and A Anichini

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Cell retargeting by bispecific monoclonal antibodies. Evidence of bypass of intratumor susceptibility to cell lysis in human melanoma.

P Nisticò, R Mortarini, L B De Monte, A Mazzocchi, M Mariani, F Malavasi, G Parmiani, P G Natali, and A Anichini

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