Immune-enhancing rnas for combination with chimeric antigen receptor therapy

A method of treating a subject having a disease associated with expression of a first antigen, e.g., a first tumor antigen, e.g., a method of treating a subject having a cancer, comprising administering to the subject an effective number of a cell (e.g., a population of cells) that expresses a chimeric antigen receptor (CAR) molecule that binds to the first antigen, e.g., the first tumor antigen (a “CAR-expressing cell”), in combination with an RNA molecule (e.g., an exogenous RNA molecule), or a nucleic acid molecule (e.g., an exogenous nucleic acid molecule) encoding an RNA molecule, wherein the RNA molecule comprises a first RNA sequence (e.g., a first exogenous RNA sequence) and a second RNA sequence (e.g., a second exogenous RNA sequence), wherein the first RNA sequence is at least 80%, 85%, or 90% complementary to the second RNA sequence, wherein the first RNA sequence is at least 20 nucleotides in length and the second RNA sequence is at least 20 nucleotides in length, wherein the RNA molecule has one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or all) of the following properties:

• (i) the RNA molecule activates a pattern recognition receptor (PRR), e.g., retinoic acid-inducible gene I (RIG-I);
• (ii) the RNA molecule activates dendritic cells (DCs), e.g., as measured by an increase in the expression of an activation marker in DCs, e.g., as measured by an increase in the expression of CD80, CD86 or Basic leucine zipper transcriptional factor ATF-like 3 (Batf3) in DCs, or as measured by the ability of the DCs to prime CD8+ T cells;
• (iii) the RNA molecule activates macrophages, e.g., as measured by an increase in the expression of an activation marker in macrophages, e.g., as measured by an increase in the expression of CD80 in macrophages;
• (iv) the RNA molecule activates T cells, e.g., as measured by an increase in the expression of an activation marker in T cells, an increase in T cell expansion, or an increase in cytokine production by T cells, e.g., as measured by an increase in the expression of CD69 or PD-1 in T cells, or as measured by IFNγ or TNFα production by T cells;
• (v) the RNA molecule enhances immune infiltration into a tumor, e.g., infiltration of DCs or T cells into a tumor;
• (vi) the RNA molecule reduces tumor growth;
• (vii) the RNA molecule increases survival of the subject;
• (viii) the RNA molecule enhances the subject's responsiveness to the CAR-expressing cells or a checkpoint modulator (e.g., an anti-PD-1 antibody molecule, an anti-PD-L1 antibody molecule, an anti-CTLA-4 antibody molecule, an anti-TIM-3 antibody molecule, or an anti-LAG-3 antibody molecule);
• (ix) the RNA molecule does not bind or does not substantially bind to SRP9 and/or SRP14;
• (x) the RNA molecule is a functional variant of a naturally-existing RN7SL1 RNA molecule, wherein the RNA molecule retains all or part of the immunogenic property of the naturally-existing RN7SL1 RNA molecule, optionally wherein the RNA molecule shows reduced binding to SRP9 and/or SRP14 compared with the naturally-existing RN7SL1 RNA molecule, e.g., the RNA molecule does not bind to or does not substantially bind to SRP9 and/or SRP14;
• (xi) the RNA molecule is not polyinosinic:polycytidylic acid (poly I:C);
• (xii) the RNA molecule does not have RNAi or antisense inhibition activity or the RNA molecule has minimal RNAi or antisense inhibition activity;
• or
• (xiii) the RNA molecule has no more than 5%, 10%, 15%, 20%, 25%, 30%, 35%, or 40% sequence identity to a naturally-existing human gene.

A method of providing an anti-cancer immune response in a subject having a cancer, comprising administering to the subject an effective number of a cell (e.g., a population of cells) that expresses a chimeric antigen receptor (CAR) molecule that binds to a first antigen, e.g., a first tumor antigen (a “CAR-expressing cell”), in combination with an RNA molecule (e.g., an exogenous RNA molecule), or a nucleic acid molecule (e.g., an exogenous nucleic acid molecule) encoding an RNA molecule, wherein the RNA molecule comprises a first RNA sequence (e.g., a first exogenous RNA sequence) and a second RNA sequence (e.g., a second exogenous RNA sequence), wherein the first RNA sequence is at least 80%, 85%, or 90% complementary to the second RNA sequence, wherein the first RNA sequence is at least 20 nucleotides in length and the second RNA sequence is at least 20 nucleotides in length, wherein the RNA molecule has one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or all) of the following properties:

• (i) the RNA molecule activates a pattern recognition receptor (PRR), e.g., retinoic acid-inducible gene I (RIG-I);
• (ii) the RNA molecule activates dendritic cells (DCs), e.g., as measured by an increase in the expression of an activation marker in DCs, e.g., as measured by an increase in the expression of CD80, CD86 or Basic leucine zipper transcriptional factor ATF-like 3 (Batf3) in DCs, or as measured by the ability of the DCs to prime CD8+ T cells;
• (iii) the RNA molecule activates macrophages, e.g., as measured by an increase in the expression of an activation marker in macrophages, e.g., as measured by an increase in the expression of CD80 in macrophages;
• (iv) the RNA molecule activates T cells, e.g., as measured by an increase in the expression of an activation marker in T cells, an increase in T cell expansion, or an increase in cytokine production by T cells, e.g., as measured by an increase in the expression of CD69 or PD-1 in T cells, or as measured by IFNγ or TNFα production by T cells;
• (v) the RNA molecule enhances immune infiltration into a tumor, e.g., infiltration of DCs or T cells into a tumor;
• (vi) the RNA molecule reduces tumor growth;
• (vii) the RNA molecule increases survival of the subject;
• (viii) the RNA molecule enhances the subject's responsiveness to the CAR-expressing cells or a checkpoint modulator (e.g., an anti-PD-1 antibody molecule, an anti-PD-L1 antibody molecule, an anti-CTLA-4 antibody molecule, an anti-TIM-3 antibody molecule, or an anti-LAG-3 antibody molecule);
• (ix) the RNA molecule does not bind or does not substantially bind to SRP9 and/or SRP14;
• (x) the RNA molecule is a functional variant of a naturally-existing RN7SL1 RNA molecule, wherein the RNA molecule retains all or part of the immunogenic property of the naturally-existing RN7SL1 RNA molecule, optionally wherein the RNA molecule shows reduced binding to SRP9 and/or SRP14 compared with the naturally-existing RN7SL1 RNA molecule, e.g., the RNA molecule does not bind to or does not substantially bind to SRP9 and/or SRP14;
• (xi) the RNA molecule is not polyinosinic:polycytidylic acid (poly I:C);
• (xii) the RNA molecule does not have RNAi or antisense inhibition activity or the RNA molecule has minimal RNAi or antisense inhibition activity;
• or
• (xiii) the RNA molecule has no more than 5%, 10%, 15%, 20%, 25%, 30%, 35%, or 40% sequence identity to a naturally-existing human gene.

A nucleic acid molecule (e.g., an exogenous nucleic acid molecule) comprising (1) a first nucleic acid molecule (e.g., a first exogenous nucleic acid molecule) encoding a chimeric antigen receptor (CAR) molecule that binds to a first antigen, e.g., a first tumor antigen, and (2) a second nucleic acid molecule (e.g., a second exogenous nucleic acid molecule) comprising an RNA molecule (e.g., an exogenous RNA molecule) or a nucleic acid molecule (e.g., an exogenous nucleic acid molecule) encoding an RNA molecule, wherein the RNA molecule comprises a first RNA sequence (e.g., a first exogenous RNA sequence) and a second RNA sequence (e.g., a second exogenous RNA sequence), wherein the first RNA sequence is at least 80%, 85%, or 90% complementary to the second RNA sequence, wherein the first RNA sequence is at least 20 nucleotides in length and the second RNA sequence is at least 20 nucleotides in length, wherein the RNA molecule has one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or all) of the following properties:

• (i) the RNA molecule activates a pattern recognition receptor (PRR), e.g., retinoic acid-inducible gene I (RIG-I);
• (ii) the RNA molecule activates dendritic cells (DCs), e.g., as measured by an increase in the expression of an activation marker in DCs, e.g., as measured by an increase in the expression of CD80, CD86 or Basic leucine zipper transcriptional factor ATF-like 3 (Batf3) in DCs, or as measured by the ability of the DCs to prime CD8+ T cells;
• (iii) the RNA molecule activates macrophages, e.g., as measured by an increase in the expression of an activation marker in macrophages, e.g., as measured by an increase in the expression of CD80 in macrophages;
• (iv) the RNA molecule activates T cells, e.g., as measured by an increase in the expression of an activation marker in T cells, an increase in T cell expansion, or an increase in cytokine production by T cells, e.g., as measured by an increase in the expression of CD69 or PD-1 in T cells, or as measured by IFNγ or TNFα production by T cells;
• (v) the RNA molecule enhances immune infiltration into a tumor, e.g., infiltration of DCs or T cells into a tumor;
• (vi) the RNA molecule reduces tumor growth;
• (vii) the RNA molecule increases survival of the subject;
• (viii) the RNA molecule enhances the subject's responsiveness to the CAR-expressing cells or a checkpoint modulator (e.g., an anti-PD-1 antibody molecule, an anti-PD-L1 antibody molecule, an anti-CTLA-4 antibody molecule, an anti-TIM-3 antibody molecule, or an anti-LAG-3 antibody molecule);
• (ix) the RNA molecule does not bind or does not substantially bind to SRP9 and/or SRP14;
• (x) the RNA molecule is a functional variant of a naturally-existing RN7SL1 RNA molecule, wherein the RNA molecule retains all or part of the immunogenic property of the naturally-existing RN7SL1 RNA molecule, optionally wherein the RNA molecule shows reduced binding to SRP9 and/or SRP14 compared with the naturally-existing RN7SL1 RNA molecule, e.g., the RNA molecule does not bind to or does not substantially bind to SRP9 and/or SRP14;
• (xi) the RNA molecule is not polyinosinic:polycytidylic acid (poly I:C);
• (xii) the RNA molecule does not have RNAi or antisense inhibition activity or the RNA molecule has minimal RNAi or antisense inhibition activity;
• or
• (xiii) the RNA molecule has no more than 5%, 10%, 15%, 20%, 25%, 30%, 35%, or 40% sequence identity to a naturally-existing human gene.

A cell, e.g., an immune cell, e.g., a T cell or NK cell, comprising (1) a first nucleic acid molecule (e.g., a first exogenous nucleic acid molecule) encoding a chimeric antigen receptor (CAR) molecule that binds to a first antigen, e.g., a first tumor antigen, and (2) a second nucleic acid molecule (e.g., a second exogenous nucleic acid molecule) comprising an RNA molecule (e.g., an exogenous RNA molecule) or a nucleic acid molecule (e.g., an exogenous nucleic acid molecule) encoding an RNA molecule, wherein the RNA molecule comprises a first RNA sequence (e.g., a first exogenous RNA sequence) and a second RNA sequence (e.g., a second exogenous RNA sequence), wherein the first RNA sequence is at least 80%, 85%, or 90% complementary to the second RNA sequence, wherein the first RNA sequence is at least 20 nucleotides in length and the second RNA sequence is at least 20 nucleotides in length, wherein the RNA molecule has one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or all) of the following properties:

• (i) the RNA molecule activates a pattern recognition receptor (PRR), e.g., retinoic acid-inducible gene I (RIG-I);
• (ii) the RNA molecule activates dendritic cells (DCs), e.g., as measured by an increase in the expression of an activation marker in DCs, e.g., as measured by an increase in the expression of CD80, CD86 or Basic leucine zipper transcriptional factor ATF-like 3 (Batf3) in DCs, or as measured by the ability of the DCs to prime CD8+ T cells;
• (iii) the RNA molecule activates macrophages, e.g., as measured by an increase in the expression of an activation marker in macrophages, e.g., as measured by an increase in the expression of CD80 in macrophages;
• (iv) the RNA molecule activates T cells, e.g., as measured by an increase in the expression of an activation marker in T cells, an increase in T cell expansion, or an increase in cytokine production by T cells, e.g., as measured by an increase in the expression of CD69 or PD-1 in T cells, or as measured by IFNγ or TNFα production by T cells;
• (v) the RNA molecule enhances immune infiltration into a tumor, e.g., infiltration of DCs or T cells into a tumor;
• (vi) the RNA molecule reduces tumor growth;
• (vii) the RNA molecule increases survival of the subject;
• (viii) the RNA molecule enhances the subject's responsiveness to the CAR-expressing cells or a checkpoint modulator (e.g., an anti-PD-1 antibody molecule, an anti-PD-L1 antibody molecule, an anti-CTLA-4 antibody molecule, an anti-TIM-3 antibody molecule, or an anti-LAG-3 antibody molecule);
• (ix) the RNA molecule does not bind or does not substantially bind to SRP9 and/or SRP14;
• (x) the RNA molecule is a functional variant of a naturally-existing RN7SL1 RNA molecule, wherein the RNA molecule retains all or part of the immunogenic property of the naturally-existing RN7SL1 RNA molecule, optionally wherein the RNA molecule shows reduced binding to SRP9 and/or SRP14 compared with the naturally-existing RN7SL1 RNA molecule, e.g., the RNA molecule does not bind to or does not substantially bind to SRP9 and/or SRP14;
• (xi) the RNA molecule is not polyinosinic:polycytidylic acid (poly I:C);
• (xii) the RNA molecule does not have RNAi or antisense inhibition activity or the RNA molecule has minimal RNAi or antisense inhibition activity;
• or
• (xiii) the RNA molecule has no more than 5%, 10%, 15%, 20%, 25%, 30%, 35%, or 40% sequence identity to a naturally-existing human gene.

A population of cells comprising (1) a first cell, e.g., an immune cell, e.g., a T cell or NK cell, comprising a first nucleic acid molecule (e.g., a first exogenous nucleic acid molecule) encoding a chimeric antigen receptor (CAR) molecule that binds to a first antigen, e.g., a first tumor antigen, and (2) a second cell comprising a second nucleic acid molecule (e.g., a second exogenous nucleic acid molecule) comprising an RNA molecule (e.g., an exogenous RNA molecule) or a nucleic acid molecule (e.g., an exogenous nucleic acid molecule) encoding an RNA molecule, wherein the RNA molecule comprises a first RNA sequence (e.g., a first exogenous RNA sequence) and a second RNA sequence (e.g., a second exogenous RNA sequence), wherein the first RNA sequence is at least 80%, 85%, or 90% complementary to the second RNA sequence, wherein the first RNA sequence is at least 20 nucleotides in length and the second RNA sequence is at least 20 nucleotides in length, wherein the RNA molecule has one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or all) of the following properties:

• (i) the RNA molecule activates a pattern recognition receptor (PRR), e.g., retinoic acid-inducible gene I (RIG-I);
• (ii) the RNA molecule activates dendritic cells (DCs), e.g., as measured by an increase in the expression of an activation marker in DCs, e.g., as measured by an increase in the expression of CD80, CD86 or Basic leucine zipper transcriptional factor ATF-like 3 (Batf3) in DCs, or as measured by the ability of the DCs to prime CD8+ T cells;
• (iii) the RNA molecule activates macrophages, e.g., as measured by an increase in the expression of an activation marker in macrophages, e.g., as measured by an increase in the expression of CD80 in macrophages;
• (iv) the RNA molecule activates T cells, e.g., as measured by an increase in the expression of an activation marker in T cells, an increase in T cell expansion, or an increase in cytokine production by T cells, e.g., as measured by an increase in the expression of CD69 or PD-1 in T cells, or as measured by IFNγ or TNFα production by T cells;
• (v) the RNA molecule enhances immune infiltration into a tumor, e.g., infiltration of DCs or T cells into a tumor;
• (vi) the RNA molecule reduces tumor growth;
• (vii) the RNA molecule increases survival of the subject;
• (viii) the RNA molecule enhances the subject's responsiveness to the CAR-expressing cells or a checkpoint modulator (e.g., an anti-PD-1 antibody molecule, an anti-PD-L1 antibody molecule, an anti-CTLA-4 antibody molecule, an anti-TIM-3 antibody molecule, or an anti-LAG-3 antibody molecule);
• (ix) the RNA molecule does not bind or does not substantially bind to SRP9 and/or SRP14;
• (x) the RNA molecule is a functional variant of a naturally-existing RN7SL1 RNA molecule, wherein the RNA molecule retains all or part of the immunogenic property of the naturally-existing RN7SL1 RNA molecule, optionally wherein the RNA molecule shows reduced binding to SRP9 and/or SRP14 compared with the naturally-existing RN7SL1 RNA molecule, e.g., the RNA molecule does not bind to or does not substantially bind to SRP9 and/or SRP14;
• (xi) the RNA molecule is not polyinosinic:polycytidylic acid (poly I:C);
• (xii) the RNA molecule does not have RNAi or antisense inhibition activity or the RNA molecule has minimal RNAi or antisense inhibition activity;
• or
• (xiii) the RNA molecule has no more than 5%, 10%, 15%, 20%, 25%, 30%, 35%, or 40% sequence identity to a naturally-existing human gene,
• optionally wherein:
• the first nucleic acid molecule and the second nucleic acid molecule are disposed in different cells.

A method of making a cell, comprising:

• (1) providing a cell, e.g., an immune cell, e.g., a T cell or NK cell, comprising a first nucleic acid molecule (e.g., a first exogenous nucleic acid molecule) encoding a chimeric antigen receptor (CAR) molecule that binds to a first antigen, e.g., a first tumor antigen, and
• (2) contacting the cell ex vivo with a second nucleic acid molecule (e.g., a second exogenous nucleic acid molecule) comprising an RNA molecule (e.g., an exogenous RNA molecule) or a nucleic acid molecule (e.g., an exogenous nucleic acid molecule) encoding an RNA molecule, wherein the RNA molecule comprises a first RNA sequence (e.g., a first exogenous RNA sequence) and a second RNA sequence (e.g., a second exogenous RNA sequence), wherein the first RNA sequence is at least 80%, 85%, or 90% complementary to the second RNA sequence, wherein the first RNA sequence is at least 20 nucleotides in length and the second RNA sequence is at least 20 nucleotides in length, wherein the RNA molecule has one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or all) of the following properties:
• (i) the RNA molecule activates a pattern recognition receptor (PRR), e.g., retinoic acid-inducible gene I (RIG-I);
• (ii) the RNA molecule activates dendritic cells (DCs), e.g., as measured by an increase in the expression of an activation marker in DCs, e.g., as measured by an increase in the expression of CD80, CD86 or Basic leucine zipper transcriptional factor ATF-like 3 (Batf3) in DCs, or as measured by the ability of the DCs to prime CD8+ T cells;
• (iii) the RNA molecule activates macrophages, e.g., as measured by an increase in the expression of an activation marker in macrophages, e.g., as measured by an increase in the expression of CD80 in macrophages;
• (iv) the RNA molecule activates T cells, e.g., as measured by an increase in the expression of an activation marker in T cells, an increase in T cell expansion, or an increase in cytokine production by T cells, e.g., as measured by an increase in the expression of CD69 or PD-1 in T cells, or as measured by IFNγ or TNFα production by T cells;
• (v) the RNA molecule enhances immune infiltration into a tumor, e.g., infiltration of DCs or T cells into a tumor;
• (vi) the RNA molecule reduces tumor growth;
• (vii) the RNA molecule increases survival of the subject;
• (viii) the RNA molecule enhances the subject's responsiveness to the CAR-expressing cells or a checkpoint modulator (e.g., an anti-PD-1 antibody molecule, an anti-PD-L1 antibody molecule, an anti-CTLA-4 antibody molecule, an anti-TIM-3 antibody molecule, or an anti-LAG-3 antibody molecule);
• (ix) the RNA molecule does not bind or does not substantially bind to SRP9 and/or SRP14;
• (x) the RNA molecule is a functional variant of a naturally-existing RN7SL1 RNA molecule, wherein the RNA molecule retains all or part of the immunogenic property of the naturally-existing RN7SL1 RNA molecule, optionally wherein the RNA molecule shows reduced binding to SRP9 and/or SRP14 compared with the naturally-existing RN7SL1 RNA molecule, e.g., the RNA molecule does not bind to or does not substantially bind to SRP9 and/or SRP14;
• (xi) the RNA molecule is not polyinosinic:polycytidylic acid (poly I:C);
• (xii) the RNA molecule does not have RNAi or antisense inhibition activity or the RNA molecule has minimal RNAi or antisense inhibition activity;
• or
• (xiii) the RNA molecule has no more than 5%, 10%, 15%, 20%, 25%, 30%, 35%, or 40% sequence identity to a naturally-existing human gene.

A kit comprising (1) a first nucleic acid molecule (e.g., a first exogenous nucleic acid molecule) encoding a chimeric antigen receptor (CAR) molecule that binds to a first antigen, e.g., a first tumor antigen, and (2) a second nucleic acid molecule (e.g., a second exogenous nucleic acid molecule) comprising an RNA molecule (e.g., an exogenous RNA molecule) or a nucleic acid molecule (e.g., an exogenous nucleic acid molecule) encoding an RNA molecule, wherein the RNA molecule comprises a first RNA sequence (e.g., a first exogenous RNA sequence) and a second RNA sequence (e.g., a second exogenous RNA sequence), wherein the first RNA sequence is at least 80%, 85%, or 90% complementary to the second RNA sequence, wherein the first RNA sequence is at least 20 nucleotides in length and the second RNA sequence is at least 20 nucleotides in length, wherein the RNA molecule has one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or all) of the following properties:

• (i) the RNA molecule activates a pattern recognition receptor (PRR), e.g., retinoic acid-inducible gene I (RIG-I);
• (ii) the RNA molecule activates dendritic cells (DCs), e.g., as measured by an increase in the expression of an activation marker in DCs, e.g., as measured by an increase in the expression of CD80, CD86 or Basic leucine zipper transcriptional factor ATF-like 3 (Batf3) in DCs, or as measured by the ability of the DCs to prime CD8+ T cells;
• (iii) the RNA molecule activates macrophages, e.g., as measured by an increase in the expression of an activation marker in macrophages, e.g., as measured by an increase in the expression of CD80 in macrophages;
• (iv) the RNA molecule activates T cells, e.g., as measured by an increase in the expression of an activation marker in T cells, an increase in T cell expansion, or an increase in cytokine production by T cells, e.g., as measured by an increase in the expression of CD69 or PD-1 in T cells, or as measured by IFNγ or TNFα production by T cells;
• (v) the RNA molecule enhances immune infiltration into a tumor, e.g., infiltration of DCs or T cells into a tumor;
• (vi) the RNA molecule reduces tumor growth;
• (vii) the RNA molecule increases survival of the subject;
• (viii) the RNA molecule enhances the subject's responsiveness to the CAR-expressing cells or a checkpoint modulator (e.g., an anti-PD-1 antibody molecule, an anti-PD-L1 antibody molecule, an anti-CTLA-4 antibody molecule, an anti-TIM-3 antibody molecule, or an anti-LAG-3 antibody molecule);
• (ix) the RNA molecule does not bind or does not substantially bind to SRP9 and/or SRP14;
• (x) the RNA molecule is a functional variant of a naturally-existing RN7SL1 RNA molecule, wherein the RNA molecule retains all or part of the immunogenic property of the naturally-existing RN7SL1 RNA molecule, optionally wherein the RNA molecule shows reduced binding to SRP9 and/or SRP14 compared with the naturally-existing RN7SL1 RNA molecule, e.g., the RNA molecule does not bind to or does not substantially bind to SRP9 and/or SRP14;
• (xi) the RNA molecule is not polyinosinic:polycytidylic acid (poly I:C);
• (xii) the RNA molecule does not have RNAi or antisense inhibition activity or the RNA molecule has minimal RNAi or antisense inhibition activity;
• or
• (xiii) the RNA molecule has no more than 5%, 10%, 15%, 20%, 25%, 30%, 35%, or 40% sequence identity to a naturally-existing human gene.

A method of evaluating or predicting a subject's responsiveness to a CAR-expressing cell therapy, comprising acquiring a value for the level or activity of an unshielded RNA molecule (e.g., an exogenous unshielded RNA molecule), wherein the RNA molecule comprises the nucleotide sequence of SEQ ID NO:

• 1, wherein the value comprises a ratio of the amount of the RNA molecule to the amount of a protein that binds to the RNA molecule, e.g., the amount of signal recognition particle 9 (SRP9) and/or signal recognition particle 14 (SRP14), wherein:
• (i) an increase in the value, as compared to a reference value, is indicative or predictive of increased responsiveness of the subject to the CAR-expressing cell therapy;
• or
• (ii) a decrease in the value, as compared to a reference value, is indicative or predictive of decreased responsiveness of the subject to the CAR-expressing cell therapy.