Compositions and methods for treatment of neoplastic disease

Abstract

The present invention comprises compositions and methods for treating a tumor or neoplastic disease in a host, The methods employ conjugates comprising superantigen polypeptides or nucleic acids with other structures that preferentially bind to tumor cells and are capable of inducing apoptosis. Also provided are superantigen-glycolipid conjugates and vesicles that are loaded onto antigen presenting cells to activate both T cells and NKT cells. Cell-based vaccines comprise tumor cells engineered to express a superantigen along with glycolipids products which, when expressed, render the cells capable of eliciting an effective anti-tumor immune response in a mammal into which these cells are introduced. Included among these compositions are tumor cells, hybrid cells of tumor cells and accessory cells, preferably dendritic cells. Also provided are T cells and NKT cells activated by the above compositions that can be administered for adoptive immunotherapy.

Description

CROSS-REFERENCE TO RELATED DOCUMENTS [0001] The Instant application is a continuation application of U.S. application Ser. No. 09 / 650,884 filed on Aug. 30, 2000 which claims priority to provisional applicaton 60 / 151,470 filed on Aug. 30, 1999. Both of the above referenced applications are incorporated herein in their entirety by reference.BACKGROUND OF THE INVENTION [0002] 1. Field of the Invention [0003] The invention relates generally to immunotherapeutic compositions and methods for treating tumors and cancer. The methods are based on the expression of superantigen (“SAg”) alone or in combination with other molecules in transfected host cells (tumor cells, accessory cells or lymphocytes). Other therapeutic methods are based on administering T cells which are activated by cells engineered to express SAg and other immunostimulatory molecules and structures. [0004] 2. Description of the Background Art [0005] Therapy of the neoplastic diseases has largely involved the use of chemothe...

AI Technical Summary

Benefits of technology

[0041] Also provided is a tumor specific T cell or NKT cell population which is activated by SAgs or the tumor cell transfectants above to produce a population of tumor specific effector cells useful in adoptive immunotherapy. After ex vivo stimulation, the T cells or NKT cells used for adoptive immunotherapy should preferentially express CD44 which indicates that they are capable of trafficking and homing to tumor sites. Additionally, the T cell population used for ex vivo immunization is engineered to overexpress the TCR variable V□ and invariant Vα sit

Problems solved by technology

However, results with these measures, while beneficial in some tumors, has had only marginal effects in many patients and little or no effect in many others, while demonstrating unacceptable toxicity.

While the initial observations of tumor killing effects with the immobilized Protein A perfusion system have been confirmed, some have obtained inconsistent results.

Second, various methods of immobilizing Protein A to solid supports have been us

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