Vaccines against cancer and infectious diseases

Abstract

A method of stimulating an immune response in a human against malignant cells or an infectious agent comprises the step of administering to the human an immunogenic amount of a primate anti-idiotype antibody or antibody fragment that acts as an immunogenic functional mimic of an antigen produced by or associated with a malignant cell or an infectious agent. Sub-human primate anti-idiotype antisera, especially from baboons, are preferred. Such anti-idiotype antibodies are used to make vaccines for inducing preventive immunity or a therapeutic immune response against tumors, viruses, bacteria, rickettsia, mycoplasma, protozoa, fungi and multicellular parasites.

Description

[0001] The present invention relates to a method of stimulating an immune response against malignant cells, pathogenic microorganisms, parasites or viruses in a patient using a primate "pseudoantigen" anti-idiotype antibody that acts as an immunogenic mimic of an antigen produced by or associated with a malignant cell, pathogenic microorganism, parasite or virus. A vaccine using such an anti-idiotype antibody is used in the foregoing method.[0002] One of the major research goals in cancer, microbial or parasite therapy is to trigger the patient's immune system to actively respond to proliferation of the tumor or infectious agent. Certain pathologies, especially cancer and virus infections, appear to be resistant to the immune system because they exhibit characteristics that result in tolerance by the host or that disable the capability of the host's immune system to combat them.[0003] The administration of anti-idiotype antibodies represents one of the most promising approaches to b...

AI Technical Summary

Benefits of technology

[0010] One object of the present invention is to provide a vaccine that will stimulate production of antibodies against normally tolerated tumor and viral antigens in human cancer patients and patients with normally intractable viral infections.

[0016] Anti-idiotype antibodies that mimic tumor or infectious agent antigens are a safe and effective component of vaccines that can induce an immune response against cancers, pathogenic microorganisms, parasites and viruses, either as a therapy for patients suffering from malignancies or infections or as a preventive measure to repress the development of cancer or to ward off an invading microorganism, parasite or virus.

[0103] It is not sufficient merely to evoke antibodies against the tumor or infectious agent antigen using an anti-idiotype antibody. A therapeutic response is required in order for the treatment to be successful, i.e., the antibodies must result in regression of the malignancy or repression, attenuation or destruction of the infectious agent. Careful selection of the tumor or infectious agent antigen and the epitope thereof which the anti-idiotype functionally mimics can enhance the efficacy of the therapeutic response, since not all tumor or infectious agent antigens will be equally effective targets for a therapeutic antibody response. Idiotype antibodies for later anti-idiotype production are preferably selected that bind to epitopes that are as specific as possible to the tumor or pathogen and non-crossreactive to normal human tissues. This will ensure that the eventual antibodies produced in response to challenge by an anti-idiotype that acts as a functional mimic of the epitope will act primarily on malignant cells or infectious agents rather than on healthy tissues. Another reason to select an epitope which is as tumor / pathogen-specific as possible is that immunization against a determinant found on normal cells could trigger a potentially harmful autoimmune response.

[0110] In particular, baboon Ab2.beta. antibodies or antibody fragments will be especially preferred. Baboon antibodies are normally well tolerated in humans and will share many common antigenic determinants, corresponding to regions of high homology to human immunoglobulin. This is shown by the fact that commercially available anti-human antisera also bind baboon antibodies. Therefore, the hypervariable regions of baboon antibodies or antibody fragments will normally provoke the bulk of the immune response, resulting in the best yield of antibodies which bind to the desired antigen.

[0112] In order to overcome the weak immunogenicity of primate anti-idiotype antibodies or fragments, especially baboon Ab2.beta., in human recipients, the immunoglobulins are preferably made more immunogenic by administration in a vaccination vehicle. Typically, they are injected in combination with an adjuvant such as Freund's complete or incomplete adjuvant, alum, or the like. Furthermore, their immunogenicity can be increased by coupling to an immunogenic carrier known to be safe in humans, e.g., an attenuated microbial agent such as tetanus toxoid, Bacillus Calmette-Guerin (BCG) or the like.

[0117] Anti-idiotype Ab2.beta. antibodies can serve as surrogate antigens and have further advantages of ease of production and often greater safety. An important further advantage of judiciously selected Ab2.beta. antibodies in an appropriate vaccine formulation is that it can be used to break tolerance to self-antigens. Thus, even those tumor and infectious agent antigens that are normally not immunogenic ("tolerized" antigens) can be mimicked, and antibodies that specifically bind to such antigens can be induced.

Problems solved by technology

Moreover, repeated immunization with foreign proteins can exert deleterious effects.