Treatment methods

An immunogenic composition comprising one or more antigens or immunogenic fragments thereof;

• wherein the one or more antigens are selected by a method comprising:
• a) obtaining, providing, or generating a library comprising bacterial cells or beads comprising a plurality of tumor antigens, wherein each bacterial cell or bead of the library comprises a different tumor antigen;
• b) contacting the bacterial cells or beads with antigen presenting cells (APCs) from a subject, wherein the APCs internalize the bacterial cells or beads;
• c) contacting the APCs with lymphocytes from the subject, under conditions suitable for activation of lymphocytes by a tumor antigen presented by one or more APCs;
• d) determining whether one or more lymphocytes are activated by one or more tumor antigens presented by one or more APCs by assessing a level of expression and/or secretion of one or more immune mediators;
• e) identifying each activating tumor antigen as (i) an antigen that stimulates the level of expression and/or secretion of one or more immune mediators, or (ii) an antigen that inhibits and/or suppresses the level of expression and/or secretion of one or more immune mediators;
• and
• f) selecting from among the identified tumor antigens (i) one or more antigens that increase a level of expression and/or secretion of one or more immune mediators associated with at least one beneficial response to cancer, (ii) one or more tumor antigens that inhibit and/or suppress a level of expression and/or secretion of one or more immune mediators associated with at least one deleterious and/or non-beneficial response to cancer, (iii) one or more antigens that increase a level of expression and/or secretion of one or more immune mediators associated with at least one deleterious and/or non-beneficial response to cancer, and/or (iv) one or more tumor antigens that inhibit and/or suppress a level of expression and/or secretion of one or more immune mediators associated with at least one beneficial response to cancer.

A method of manufacturing an immunogenic composition, the method comprising:

• combining one or more selected antigens or immunogenic fragments thereof and a carrier;
• wherein the one or more selected antigens are selected by a method comprising:
• a) obtaining, providing, or generating a library comprising bacterial cells or beads comprising a plurality of tumor antigens, wherein each bacterial cell or bead of the library comprises a different tumor antigen;
• b) contacting the bacterial cells or beads with antigen presenting cells (APCs) from a subject, wherein the APCs internalize the bacterial cells or beads;
• c) contacting the APCs with lymphocytes from the subject, under conditions suitable for activation of lymphocytes by a tumor antigen presented by one or more APCs;
• d) determining whether one or more lymphocytes are activated by one or more tumor antigens presented by one or more APCs by assessing a level of expression and/or secretion of one or more immune mediators;
• e) identifying each activating tumor antigen as (i) an antigen that stimulates the level of expression and/or secretion of one or more immune mediators, or (ii) an antigen that inhibits and/or suppresses the level of expression and/or secretion of one or more immune mediators;
• and
• f) selecting from among the identified tumor antigens (i) one or more antigens that increase a level of expression and/or secretion of one or more immune mediators associated with at least one beneficial response to cancer, (ii) one or more tumor antigens that inhibit and/or suppress a level of expression and/or secretion of one or more immune mediators associated with at least one deleterious and/or non-beneficial response to cancer, (iii) one or more antigens that increase a level of expression and/or secretion of one or more immune mediators associated with at least one deleterious and/or non-beneficial response to cancer, and/or (iv) one or more tumor antigens that inhibit and/or suppress a level of expression and/or secretion of one or more immune mediators associated with at least one beneficial response to cancer.

A method of identifying a subject as a candidate for cancer therapy, the method comprising:

• 1) obtaining a subject response profile, wherein the subject response profile is generated by:
• a) obtaining, providing, or generating a library comprising bacterial cells or beads comprising a plurality of tumor antigens, wherein each bacterial cell or bead of the library comprises a different tumor antigen;
• b) contacting the bacterial cells or beads with antigen presenting cells (APCs) from a subject, wherein the APCs internalize the bacterial cells or beads;
• c) contacting the APCs with lymphocytes from the subject, under conditions suitable for activation of lymphocytes by a tumor antigen presented by one or more APCs;
• d) determining whether one or more lymphocytes are activated by one or more tumor antigens presented by one or more APCs by assessing a level of expression and/or secretion of one or more immune mediators;
• e) identifying each activating tumor antigen as (i) an antigen that stimulates the level of expression and/or secretion of one or more immune mediators, or (ii) an antigen that inhibits and/or suppresses the level of expression and/or secretion of one or more immune mediators, to obtain or generate a subject response profile;
• and
• 2) determining, based on one or more characteristics of the subject response profile, whether the subject is a candidate subject for initiation, continuation, modification, discontinuation or non-initiation of a cancer therapy.