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-10383924-B2
Publication Date
2019-08-20
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 improve the induction of therapeutic immune responses and to prevent, ameliorate, and/or treat diseases such as cancer and infectious diseases. Specifically, it involves the use of recombinant virus immunotherapeutic vaccines and yeast-based immunotherapeutic vaccines, each targeting the same antigen or immunogenic domain. These vaccines induce distinct T-cell populations characterized by unique cytokine responses, gene expression profiles, and T-cell receptor (TCR) phenotypes. The concurrent administration of these vaccines results in a more diverse T-cell population and improved therapeutic efficacy, including enhanced antitumor effects in cancer models.
The problem being addressed is that despite advances in immunotherapy, there remains an urgent need for safe and effective immunotherapy strategies and adjuvants for various diseases, particularly those caused by cancer and intracellular pathogens. Many vaccines, especially subunit vaccines, primarily stimulate humoral immunity and fail to elicit protective cell-mediated immunity which is desired for treating cancers and infectious diseases. Although diversified prime-boost regimens using different viral vectors targeting the same antigen have been used to amplify T-cell responses, concurrent administration of two different vaccine platforms targeting the same antigen had not been reported and historically was thought not to improve efficacy.
The invention demonstrates, contrary to previous reports, that vaccines using different vectors induce phenotypically and functionally distinct T-cell populations even when targeting the same antigen. Recombinant vaccinia virus expressing costimulatory molecules and cancer antigens induces a Th1 response and CD8+ T-cells with a Tc1 phenotype, while yeast-based vaccines induce a mixed Th1/Th2 response and CD8+ T-cells with a mixed Tc1/Tc2 phenotype. This difference is attributed to both the vector and antigen delivery methods. Importantly, the concurrent administration of these two compositions was shown to improve antitumor efficacy, representing a novel immunotherapy strategy that maximizes immune response by inducing diverse T-cell populations at the initial vaccination.
Claims Coverage
The patent includes one independent claim describing a method of cancer treatment and use claims directed to kits comprising immunotherapy compositions. The main inventive features cover the concurrent administration of specified immunotherapy compositions, composition details, and method improvements.
Concurrent administration of two distinct immunotherapy compositions targeting the same antigen
A method comprising administering two immunotherapy compositions within one dosing period to prime the immune system concurrently, the compositions including a first recombinant vaccinia virus expressing costimulatory molecules B7-1, ICAM-1 and LFA-3 and nucleic acids encoding carcinoembryonic antigen (CEA) or immunogenic domain thereof, and a second whole inactivated yeast recombinantly expressing CEA or immunogenic domain thereof; resulting in reduced tumor burden, inhibited tumor growth, and/or induction of a therapeutic immune response against CEA.
Administration to different sites and boosting regimens
The first and second compositions can be administered to different sites in the individual. The method may include boosting with one or both compositions and optionally with a third immunotherapy composition comprising a recombinant virus different from the first.
Inclusion of specific epitopes and viral strains
The CEA antigen can include a CAP1-6D epitope. The vaccinia virus may be from modified vaccinia Ankara (MVA) or vaccinia-Wyeth strain. The whole inactivated yeast may be heat-killed and derived from Saccharomyces.
Kit containing specified immunotherapy compositions
A kit comprising a first immunotherapy composition with recombinant vaccinia virus encoding B7-1, ICAM-1, LFA-3 and human CEA or immunogenic domain, and a second composition comprising whole inactivated yeast recombinantly expressing human CEA or immunogenic domain. The kit may also include a third immunotherapy composition with recombinant fowlpox virus encoding B7-1, ICAM-1, LFA-3 and CEA, and recombinant fowlpox virus encoding GM-CSF.
Use of recombinant fowlpox virus encoding GM-CSF
The first and/or third immunotherapy compositions may further comprise granulocyte-macrophage colony-stimulating factor (GM-CSF) provided by recombinant fowlpox virus encoding GM-CSF.
Combination therapy with chemotherapy and/or radiation
The method may further include treatment of the individual with chemotherapy and/or radiation therapy in addition to the concurrent immunotherapy compositions.
The claims cover methods and kits for concurrently administering a recombinant vaccinia virus-based immunotherapy composition and a yeast-based immunotherapy composition both targeting CEA. The compositions include specific immunostimulatory molecules and epitopes, administration protocols including different sites and boosting, and optional inclusion of recombinant fowlpox viruses encoding costimulatory molecules and GM-CSF. The invention encompasses concurrent administration to reduce tumor burden, inhibit tumor growth, and induce therapeutic immune responses in cancer patients.
Stated Advantages
Concurrent administration of two distinct vaccine platforms targeting the same antigen induces a more diverse and phenotypically distinct T-cell population.
The combined use of recombinant virus-based and yeast-based immunotherapy compositions substantially improves antitumor efficacy compared to either vaccine alone.
The invention allows for effective concurrent use of different immunotherapy vectors targeting the same antigen, eliminating the need for prior diversified prime-boost schedules.
The approach is safe and potentially more effective in eliciting therapeutic immune responses in cancer and infectious diseases by harnessing distinct immune mechanisms from each vector.
Documented Applications
Prevention, amelioration, or treatment of cancer by reducing tumor burden, inhibiting tumor growth, and increasing survival in individuals with cancer.
Induction of therapeutic immune responses against cancer antigens, particularly carcinoembryonic antigen (CEA) and immunogenic domains thereof.
Use in treatment regimens combined with chemotherapy and/or radiation therapy for enhanced efficacy.
Treatment of infectious diseases by inducing immune responses against antigens associated with pathogens including viral, bacterial, fungal, protozoan, helminth, and ectoparasite antigens.
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