Harvard College

University System of Maryland

Dana-farber-cancer Institute Inc.

Sivasubramanina Baskar

Gordon James Freeman

Laurie H Glimcher

Lee M Nadler

Suzanne Ostrand-Rosenberg

Tumor cells modified to express a T cell costimulatory molecule are disclosed. In one embodiment, the costimulatory molecule is a CD28/CTLA4 ligand, preferably a B lymphocyte antigen B7. The tumor cells of the invention can be modified by transfection with nucleic acid encoding a T cell costimulatory molecule, by using an agent which induces or increases expression of a T cell costimulatory molecule on the tumor cell surface or by coupling a T cell costimulatory molecule to the tumor cell surface. Tumor cells further modified to express MHC class I and/or class II molecules or in which expression of an MHC associated protein, the invariant chain, is inhibited are also disclosed. The modified tumor cells of the invention can be used in methods for treating-a patient with a tumor, preventing or inhibiting metastatic spread of a tumor or preventing or inhibiting recurrence of a tumor. A method for specifically inducing a CD4T cell response against a tumor and a method for treating a tumor by modification of tumor cells in vivo are disclosed.

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Willcott City, MD, United States of America

Sivasubramanina Baskar