Thomas Jefferson University

Other

David Berd

Laurence C Eisenlohr

Michael J Mastrangelo

Edmund C Lattime

Lorne F Erdile

Margalit B Mokyr

A method of preserving haptenized tumor cells is described. The method employs a freezing medium containing an effective amount of sucrose and human serum albumin in an isotonic buffered saline solution. Cryogenically preserving haptenized cells in such a medium has been found to maintain the integrity of the tumor cells during storage. The haptenized tumor cells also retain cell-associated antigens and haptens, and are as immunogenic, i.e., capable of inducing immunotherapeutic response, as fresh vaccine in a mouse model of metastatic disease. In a specific embodiment, haptenized cells are exposed to a solution of 8% sucrose, 10% human serum albumin in Hank's buffered solution, and then frozen to &#x2212;80&#xb0; C. overnight and then stored in a liquid nitrogen freezer. Methods of storing haptenized tumor cells and compositions are also provided.

Cryopreservation of haptenized tumor cells

The present invention is directed to a treatment for cancer. Compositions and methods of treating cancer are included in the scope of the present invention. The compositions of the present invention include a composition prepared from tumor cells or tumor cell extracts. The methods of the present invention are directed to treating cancer comprising administering a therapeutically effective amount of a composition comprising tumor cells and/or tumor cell extracts.

Composition and method of using tumor cells

The present invention is directed to compositions and methods of treating cancer. The compositions of the present invention include a composition prepared from a tumor cell which is hapten modified and syngeneic to the type of tumor to be treated. The composition has the properties, when administered with an adjuvant to a human suffering from a malignant tumor of the same type as said tumor cell, of eliciting T lymphocytes that infiltrate the tumor of said human, of eliciting an inflammatory immune response against the tumor of said human, and of eliciting a delayed-type hypersensitivity response to the tumor of said human. The methods of the present invention are directed to treating cancer comprising administering a therapeutically effective amount of a composition comprising a tumor cell.

Composition and method of using carcinoma tumor cells

This invention relates to compositions comprising haptenized tumor cells and extracts thereof, methods for preparing the compositions, vaccines comprising such haptenized tumor cells, and methods for treating cancer with such vaccines. In a specific embodiment, melanoma cells are haptenized with a dinitrophenyl group, and used for treatment of melanoma patients having metastatic disease. Preferably, patients are given a first vaccine dose containing haptenized cells to 'prime' the immune system. Subsequently, patients are injected with an immunomodulatory compound such as cyclophosphamide. In a preferred embodiment, an appropriate time period after the 'priming' vaccine dose, additional vaccine doses containing a mixture of haptenized cells and an adjuvant are administered. The described treatment plan is more effective for eliciting favorable anti-tumor immune responses.

Low dose haptenized tumor cell and tumor cell extract immunotherapy

A method of inducing expression of immune active cytokines in tumors in situ is provided wherein a vaccinia virus vector capable of inducing expression of a selected cytokine is generated and injected into a tumor so that cells of the tumor express the selected cytokine. A method of enhancing immunity in a host by administration of a vaccinia virus vector is also provided. Methods of treating cancer by administration of these vaccinia virus vectors are also provided.

Method of inducing an immune response using vaccinia virus recombinants

The present invention is directed to compositions containing hapten-modified tumor cells and extracts and methods of treating cancer by administering a therapeutically effective amount of a composition containing a tumor cell or tumor cell extract to a subject in need of such treatment. The tumor cells and extracts of the invention and compositions thereof are capable of eliciting T lymphocytes that have a property of infiltrating a mammalian tumor, eliciting an inflammatory immune response to a mammalian tumor, eliciting a delayed-type hypersensitivity response to a mammalian tumor and/or stimulating T lymphocytes in vitro. The invention also relates to an effective vaccination schedule useful for inducing an antitumor response in a mammalian patient suffering from cancer by inducing at least one of the following: tumor necrosis, tumor regression, tumor inflammation, tumor infiltration by activated T lymphocytes, delayed-type hypersensitivity response, and prolongation of patient survival.

Composition comprising tumor cells and extracts and method of using thereof

The present invention is directed to mammalian cells conjugated to a hapten and methods of making and using thereof. Conjugating hapten to mammalian cells is a useful way of preventing cells from growing and may be used in the place of any conventional treatment, for example, irradiation. Thus, the invention relates to mammalian cells in general, for example human cells, which cells are in substantially no growth phase and a method of placing the cells in a substantially no growth phase by conjugating them to a hapten. The invention is further directed to compositions containing hapten-modified tumor cells and extracts and methods of treating cancer by administering a therapeutically effective amount of a composition containing a tumor cell or tumor cell extract to a subject in need of such treatment. The tumor cells and extracts of the invention and compositions thereof are capable of eliciting T lymphocytes that have a property of infiltrating a mammalian tumor, eliciting an inflammatory immune response to a mammalian tumor, eliciting a delayed-type hypersensitivity response to a mammalian tumor and/or stimulating T lymphocytes in vitro. The invention also relates to an effective vaccination schedule useful for inducing an antitumor response in a mammalian patient suffering from cancer by inducing at least one of the following: tumor necrosis, tumor regression, tumor inflammation, tumor infiltration by activated T lymphocytes, delayed-type hypersensitivity response, and prolongation of patient survival. Furthermore, the invention relates to an improved, simplified and economical method for preparing the hapten-conjugated tumor cells for administration as a vaccine by eliminating a separate step of treating cells (by irradiation, for example) to place them in a no growth phase.

Hapten-conjugated mammalian cells and methods of making and using thereof

Method of using haptenized ovarian carcinoma tumor cells

A composition comprising an isotonic, buffered aqueous medium containing an optimized concentration of human serum albumin has been found to stabilize irradiated, haptenized tumor cells stored for some period of time after haptenization. In specific embodiments, the viability of the haptenized tumor cells stored in a composition of the invention ranged from about 60% to about 100% greater than the cell viability of cells stored in a prior art solution. In a specific embodiment, 1% human serum albumin in Hank's Buffered Salt Solution was found to stabilize haptenized melanoma cells. Methods of storing haptenized tumor cells and vaccine preparations are also provided.

Compositions for preserving haptenized tumor cells for use in vaccines

The invention is a haptenized tumor vaccine for the treatment of cancer. Treatment of cancer patients with an autologous, vaccine preceded by low dose cyclophosphamide (CY) induces delayed-type hypersensitivity (DTH) to melanoma cells, and in some cases, regression of metastatic tumors. The efficiency of the process has been increased by immunizing with tumor cells conjugated to the hapten such as DNP, TNP or AED. Additional embodiments of the vaccine include: 1) combining the vaccine with immunomodulating drugs, such as, interleukin-2 (IL2); and 2) purifying the active components of the vaccine by extracting antigens from cancer cells to produce a chemically-defined, haptenated vaccine. The treatment may also be extended to include other types of human cancer.

Growing community of inventors

Wyncote, PA, United States of America

David Berd