Combination immunotherapy compositions against cancer and methods
Inventors
Hodge, James • Schlom, Jeffrey • Franzusoff, Alex
Assignees
GlobeImmune Inc • US Department of Health and Human Services
Publication Number
US-12076382-B2
Publication Date
2024-09-03
Expiration Date
2030-04-16
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Abstract
Disclosed are immunotherapeutic compositions and the concurrent use of combinations of such compositions for the improved induction of therapeutic immune responses and/or for the prevention, amelioration and/or treatment of disease, including, but not limited to, cancer and infectious disease.
Core Innovation
The invention relates to the concurrent use of two different immunotherapeutic compositions to induce therapeutic immune responses and/or to prevent, ameliorate, and/or treat disease, including cancer and infectious diseases. Specifically, the compositions comprise recombinant virus immunotherapeutic vaccines and yeast-based immunotherapeutic vaccines that target the same antigen or immunogenic domain thereof. It has been demonstrated that both vaccine vectors and antigens contribute to inducing T-cell populations with shared and unique cytokine responses, gene expression profiles, and T-cell receptor phenotypes. This concurrent administration induces distinct T-cell populations and improves therapeutic efficacy.
The problem addressed is the need to develop safe and effective immunotherapy strategies and adjuvants for diseases including cancer and infectious diseases. Many existing vaccines, especially subunit and killed or attenuated pathogen vaccines, elicit strong humoral immune responses but often fail to induce protective cell-mediated immunity important for treating cancers and some infectious diseases. Prior vaccine strategies have used diversified prime-boost regimens with different vectors targeting the same antigen, but concurrent use of different vaccine platforms targeting the same antigen had not been described. There remains an urgent need to improve immunotherapy approaches that effectively induce diverse and protective T-cell responses.
This invention discloses that two immunotherapeutic vaccines targeting the same antigen but using different platforms (recombinant virus and yeast) induce phenotypically and functionally distinct T-cell populations. The mechanisms differ in antigen delivery and immune activation leading to distinct Th1, Th2, Tc1, and Tc2 phenotypes and distinct TCR repertoires. Importantly, concurrent administration of these vaccines results in substantially higher antitumor efficacy in a preclinical model by inducing a more diverse T-cell population. This concurrent administration strategy differs from traditional prime-boost regimens and maximizes immune response from the initial vaccination onward.
Claims Coverage
The claims disclose one independent pharmaceutical composition claim describing a combination immunotherapy composition comprising a recombinant adenovirus and a yeast-based immunotherapy composition.
Combination of a recombinant Ad5 adenovirus and yeast-based immunotherapy composition
The composition comprises two immunotherapy compositions administered within a dosing period: (a) a first immunotherapy composition comprising a recombinant Ad5 adenovirus encoding one or more peptides derived from one or more proteins; and (b) a second immunotherapy composition comprising either whole inactivated yeast or yeast lysate.
Yeast-based immunotherapy composition properties
The second immunotherapy composition comprises one or more peptides and may be derived from the same one or more proteins as the first composition. The yeast is whole, heat-killed, and derived from Saccharomyces or Pichia species.
Formulation and administration of compositions
The first and second immunotherapy compositions are formulated for administration either to different sites, the same site, or adjacent sites in the individual, and may be administered intratumorally. The compositions may be formulated for simultaneous or sequential administration within a dosing period of no more than 2 days, preferably shorter (down to minutes).
Optional third immunotherapy composition
The pharmaceutical composition may further comprise a third immunotherapy composition comprising at least one of a recombinant virus and whole inactivated recombinant yeast or lysate thereof, expressing peptides different from those in the first composition.
Inclusion of additional therapeutic agents or immunostimulatory molecules
The pharmaceutical composition may further comprise chemotherapy and/or radiation therapy, one or more nucleic acids encoding costimulatory molecules (e.g., B7.1, B7.2, ICAM-1, LFA-3, 4-1BBL, CD59, VCAM-1, CD40, CD70, OX-40L), cytokines or chemokines (e.g., IL-2, GM-CSF, TNF-α, IFN-γ), and antibodies such as anti-CTLA-4, anti-PD-L1, anti-PD-1, or anti-PD-L2 antibodies.
The claims broadly cover a pharmaceutical composition comprising concurrently administered recombinant adenovirus and yeast-based immunotherapy compositions targeting peptides from the same or different proteins, formulated for various administration strategies and optionally including additional immunostimulatory molecules or therapeutic agents.
Stated Advantages
Concurrent administration of two distinct vaccine platforms targeting the same antigen induces a more diverse T-cell population and results in improved antitumor efficacy.
The combined vaccines elicit distinct and complementary cytokine profiles and T-cell receptor repertoires, enhancing immune response.
Concurrent administration can eliminate the need for prime-boost schedules by maximizing immune response from the initial vaccination.
Documented Applications
Prevention, amelioration, and treatment of cancer, including induction of therapeutic immune responses against cancer antigens and increasing survival of individuals with cancer.
Treatment of diseases caused by infectious agents including viruses, bacteria, fungi, parasites, and protozoa by inducing antigen-specific immune responses.
Use in combination with chemotherapy, radiation therapy, and other biological response modifiers for enhanced disease treatment.
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