Combination treatment regimes for treating cancer
AssigneesBarinthus Biotherapeutics North America, Inc., The United States of America, as represented by the Secretary, Department of Health and Human Servic, The Chancellor, Masters and Scholars of the University of Oxford
InventorsGeoffrey Martin Lynn, Christopher Martin O'Brien Garliss, Andrew Scott Ishizuka, Faezzah Baharom, Robert Alan Seder, Ramiro Andrei Ramirez-Valdez
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Abstract
The present disclosure relates to methods of treating cancer in subjects by a two-part treatment regime comprising a first treatment that provides antigen-specific CD4+ and/or CD8+ T cells in the subject and a second treatment, administered after a time interval, that induces systemic and/or tumor-specific inflammation in the subject.
Claims34
A method for treating a cancer in a subject in need thereof, comprising (a) administering a first treatment comprising an antigen that provides antigen-specific CD4+ and/or CD8+ T cells in the subject, and (b) following a time interval (T), administering a second treatment that induces systemic and/or tumor specific inflammation in the subject.
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A method for treating cancer in a subject in need thereof, comprising (a) administering a first treatment by IM or IV and (b) following a time interval, administering a second treatment by IV, wherein the first treatment comprises a first peptide antigen conjugate of formula S-[E1]-A-[E2]-[U]-H-[D] or of formula PEG-[E1]-A-[E2]-[U]-H-[D], wherein:
- A is a peptide antigen,
- H is a hydrophobic molecule,
- S is a solubilizing block,
- PEG is polyethylene glycol,
- E1 is an N-terminal extension,
- E2 is a C-terminal extension,
- U is a linker,
- D is a drug molecule,
- [ ] denotes that the group is optional, and
- a dash (-) indicates a covalent linkage,
- wherein the second treatment comprises a second peptide antigen conjugate of formula PEG-[E1]-A-[E2]-[U]-H-[D], and wherein the second peptide antigen conjugate comprises or is administered together with (a) one or more of a TLR-3, TLR-7, TLR-8, TLR-7/8, TLR-9, MDA5, RIG1, or STING agonist, and/or (b) a molecule that induces Flt3, IL-12, and/or type-I IFN signaling;
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- optionally wherein the first treatment provides antigen-specific CD4+ and/or CD8+ T cells in the subject and the second treatment induces systemic and/or tumor specific inflammation in the subject.
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A method for treating cancer in a subject in need thereof, comprising (a) administering a first treatment by IV or IM, and (b) following a time interval, administering a second treatment by IV, wherein the first treatment comprises a first peptide antigen conjugate of formula S-[E1]-A-[E2]-[U]-H-[D] or of formula PEG-[E1]-A-[E2]-[U]-H-[D], wherein:
- A is a peptide antigen,
- H is a hydrophobic molecule,
- S is a solubilizing block,
- PEG is polyethylene glycol,
- E1 is an N-terminal extension,
- E2 is a C-terminal extension,
- U is a linker,
- D is a drug molecule,
- [ ] denotes that the group is optional, and
- a dash (-) indicates a covalent linkage,
- optionally wherein the peptide antigen conjugate has a net electrostatic charge greater than or equal to +3 or less than or equal to −3 in an aqueous buffer at a pH of 7.4, and optionally wherein the hydrophobic molecule (H) is water insoluble at pH 7.4;
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- wherein the second treatment comprises a polynucleotide optionally encoding an antigen, wherein the polynucleotide is optionally an adenovirus, adeno-associated virus, rhabdovirus, ChAdOx, MVA virus, DNA vector, or RNA vector;
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- optionally wherein the first treatment provides antigen-specific CD4+ and/or CD8+ T cells in the subject and the second treatment induces systemic and/or tumor specific inflammation in the subject.
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A method for treating cancer in a subject in need thereof, comprising administering an adoptive cell therapy (ACT) and intravenously administering a vaccine, wherein the ACT and the vaccine are administered sequentially such that the vaccine is administered from 3 days prior to administration of the ACT to 14 days following administration of the ACT.
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A method for treating cancer in a subject in need thereof, comprising administering an adoptive cell therapy (ACT) and intravenously administering an immunostimulant, wherein the ACT and the immunostimulant are administered sequentially such that the immunostimulant is administered from 3 days prior to administration of the ACT to 14 days following administration of the ACT, wherein the immunostimulant comprises:
- (a) one or more of a TLR-3, TLR-7, TLR-8, TLR-7/8, TLR-9, MDA5, RIG1, or STING agonist, (b) a molecule that induces Flt3, IL-12, and/or type-I IFN signaling, and/or (c) an amphiphile, such as such as an amphiphile of formula S-[B]-[U]-H-[D], wherein:
- S is a solubilizing block,
- H is a hydrophobic block,
- B is an extension,
- U is a linker
- D is a drug molecule,
- [ ] denotes that the group is optional, and
- a dash (-) indicates a covalent linkage.
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Dependencies are inferred from the claim text.