Melanoma vaccine and methods of making and using same

Abstract

An immunotherapeutic vaccine providing antigen presenting cells that have been pulsed with a disrupted cell preparation which includes enucleated cytosol and cell membranes of cancer cells infected with a recombinant vaccinia virus encoding at least one immunostimulating molecule. In a preferred embodiment, the vaccine includes autologous dendritic / monocytic cells (DC / M) that present a mixture of antigens (present in the enucleated cytosol and cell membranes) from melanoma cell lines that have been infected with a recombinant vaccinia virus encoding IL-2. In another of the preferred embodiments, the enucleated cytosol and cell membranes are from melanoma cells harvested from the patient to be treated. A method of making the vaccine and methods of using the vaccine to stimulate an anti-cancer immune response and to treat a patient with a cancer are also described.

Description

FIELD OF THE INVENTION [0001] The invention generally relates to an improved therapeutic vaccine useful for treatment and prevention of a cancer. Disclosed are a cancer vaccine, and methods of making and using such a vaccine in a host diagnosed with a cancer. The vaccine as used in accordance with the present invention comprises a new administration schedule and ingredients such as recombinant IL-2 encoding vaccinia virus and autologous dendritic / monocytic cells pulsed with melanoma antigens derived from cancerous melanoma cell lines expressing at least two HLA class I A antigens. BACKGROUND OF THE INVENTION [0002] The incidence of malignant melanoma has increased at an alarming rate over the past few decades, and indications are that the incidence of this deadly disease will continue to rise in the future. As melanoma is known to be refractory to conventional chemotherapy or radiotherapy, several alternative treatment approaches have been used for treatment of this variety of skin ...

AI Technical Summary

Benefits of technology

[0024] The present invention provides a therapeutic composition made up of antigen presenting cells that have been pulsed with a disrupted cell preparation. The disrupted cell preparation includes enucleated cytosol and cell membranes of cancer cells that have been infected with a recombinant vaccinia virus that encodes for at least one immunostimulating molecule. In one embodiment, the invention provides a therapeutic vaccine in which autologous dendritic/monocytic cells (DC/M) present a mixture of antigens (present in a preparation of enucleated cytosol and cell membranes) that are

Problems solved by technology

Although a clinical benefit was seen in several subsets of patients, especially in young male patients with stage III (AJCC) melanoma, the vaccine did not produce a significant benefit for melanoma patients when tested as a surgical adjuvant therapy in a recently completed phase III clinical trial.

Although such immunotherapy trials with these vaccines have shown encouraging results in some patients, e.g., partial regression of melanoma, delay in the appearance of recurrent melanoma, and an increase in overall survival as compared to standard therapy or surgery, none of the methods so far have been entirely satisfactory.

However, bolus injection with a high dose of cytokines generally produces significant toxicity while low dose continuous infusion is inconvenient.

Thus, the success of recombinant IL-2 in gene therapy strategies is unpredictable.

In addition, it appears that co-administration of lymphokine-activated killer (LAK) cells, generated ex vivo with rIL-2, does not enhance the response rates achieved with rIL-2 alone.

For that reason, IL-2-based therapy has not proven to be very effective.

In addition, the doses of IL-2 required by these IL-2 treatment methods appear toxic to treated patients.

Thus, despite the fact that vaccination with autologous DCs was determined to be safe, the efficacy of such vaccines was not any better than with conventional melanoma vaccines.

This and other similar approaches have failed to improve DC-based vaccines and to enhance the chances of survival of melanoma patients.

Despite many studies relating to melanoma vaccine development, so far little real progress has been achieved.

Thus, while multiple approaches to melanoma (and cancer generally) have been undertaken during the last twenty years, and some progress made, the problem has remained.

Melanoma continues to be on the rise and refractory to available therapies.

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