Abstract: The present disclosure provided compositions and methods for treating solid tumors. In certain aspects, the disclosure provides modified immune cells (i.e. CAR T cells) wherein CD5 has been disrupted or knocked-out.

Abstract: Among the various aspects of the present disclosure is the provision of methods of detecting and treating immunotherapy-resistant B cell malignancies. Methods of detection include detecting a glycosylation state of CD19 or detecting expression or activity of SPPL3 in malignant B cells, comparing to a reference state or value, and determining that the B cell malignancy is resistant to immunotherapy if the glycosylation state of CD19 or expression or activity of SPPL3 is substantially increased or decreased relative to corresponding reference levels. Also provided are therapeutic agents capable of modulating CD19 glycosylation or SPPL3 expression or activity for treatment of B cell malignancies in combination with CD19-targeted immunotherapies.

Abstract: The present invention includes compositions and methods for treating T cell lymphomas and leukemias. In certain aspects, the compositions and methods include CAR T cells targeting CD2, CD5, or CD7 and modified cells wherein CD2, CD5, or CD7 has been knocked-out.

Abstract: The invention provides compositions and methods for treating diseases associated with expression of BCMA. The invention also relates to chimeric antigen receptor (CAR) specific to BCMA vectors encoding the same, and recombinant T cells comprising the BCMA CAR. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises a BCMA binding domain.

Abstract: Compositions and methods for inhibiting, treating, and/or preventing a B-cell neoplasm are provided.

Abstract: Disclosed herein are a novel antibody and an antigen binding fragment thereof that targets CD30 to treat cancer, a chimeric antigen receptor, and a use thereof. The antibody, which binds specifically to CD30 that is highly expressed in cancer cells (specifically blood cancer), is very low in sequence homology with the CDR sequences of conventional CD30 targeting antibodies and thus has a unique sequence. Cells that express the chimeric antigen receptor including the anti-CD30 antibody or the antigen binding fragment responds to CD30-expressing positive cells to induce immune cell activity, thus finding advantageous applications as a CAR-immune cell product.

Abstract: The present invention relates to compositions and methods for treating or preventing a hematologic cancer or autoimmune disease of a mammal using anti-BCR CARs. One aspect includes a modified T cell and pharmaceutical compositions comprising the modified cells for adoptive cell therapy and treating a cancer or autoimmune disease associated with B cells comprising enriched stereotyped BCRs.

Abstract: The present disclosure provides modified cell(s), i.e., immune cell(s) or precursor cell(s) thereof, wherein the cell(s) are engineered to express a) a chimeric antigen receptor (CAR), and b) a variant of a B-cell lymphoma 2 (Bcl-2) family protein, wherein the variant confers resistance to a cytotoxic inhibitor of the Bcl-2 family protein. Also provided are methods and uses of the modified cells, e.g., for treating at least one sign and/or symptom of cancer. Related nucleic acids, vectors, and pharmaceutical compositions are also provided.

Abstract: The present disclosure relates to compositions and methods for predicting cancer survival or toxicity in a subject receiving a chimeric antigen receptor (CAR) T cell therapy. The present disclosure further discloses compositions, e.g., pharmaceutical compositions, and methods for treating said subject.

Abstract: The present invention includes compositions and methods comprising CART cells with SHP-1 and/or SHP-2 genes knocked out.

Abstract: The invention provides compositions and methods for treating diseases associated with expression of CD20 or CD22. The invention also relates to chimeric antigen receptor (CAR) specific to CD20 or CD22, vectors encoding the same, and recombinant T or natural killer (NK) cells comprising the CD20 CAR or CD22 CAR. The invention also includes methods of administering a genetically modified T cell or NK cell expressing a CAR that comprises a CD20 or CD22 binding domain.

Abstract: The present invention includes compositions and methods for treating T cell lymphomas and leukemias. In certain aspects, the compositions and methods include CAR T cells targeting CD2, CD5, or CD7 and modified cells wherein CD2, CD5, or CD7 has been knocked-out.

Abstract: The invention provides compositions and methods for treating diseases associated with expression of CD20 or CD22. The invention also relates to chimeric antigen receptor (CAR) specific to CD20 or CD22, vectors encoding the same, and recombinant T or natural killer (NK) cells comprising the CD20 CAR or CD22 CAR. The invention also includes methods of administering a genetically modified T cell or NK cell expressing a CAR that comprises a CD20 or CD22 binding domain.

Abstract: The invention provides compositions and methods for treating diseases associated with expression of CD19, e.g., by administering a recombinant T cell comprising the CD19 CAR as described herein, in combination with one or more B-cell inhibitors, e.g., inhibitors of one or more of CD10, CD20, CD22, CD34, CD123, FLT-3, ROR1, CD79b, CD179b, or CD79a. The disclosure additionally features novel antigen binding domains and CAR molecules directed to CD20 and CD22, and uses, e.g., as monotherapies or in combination therapies. The invention also provides kits and compositions described herein.

Abstract: The present invention includes compositions and methods for treating T cell lymphomas and leukemias. In certain aspects, the compositions and methods include CAR T cells targeting CD2, CD5, or CD7 and modified cells wherein CD2, CD5, or CD7 has been knocked-out.

Abstract: The invention provides compositions and methods for treating diseases associated with expression of CD123. The invention also relates to chimeric antigen receptor (CAR) specific to CD123, vectors encoding the same, and recombinant cells comprising the CD123 CAR. The invention also includes methods of administering a genetically modified cell expressing a CAR that comprises a CD123 binding domain.

Abstract: The present invention includes compositions and methods for treating T cell lymphomas and leukemias. In certain aspects, the compositions and methods include CAR T cells targeting CD2, CD5, or CD7 and modified cells wherein CD2, CD5, or CD7 has been knocked-out.

Abstract: The invention provides compositions and methods for treating diseases associated with expression of CD123. The invention also relates to chimeric antigen receptor (CAR) specific to CD123, vectors encoding the same, and recombinant cells comprising the CD123 CAR. The invention also includes methods of administering a genetically modified cell expressing a CAR that comprises a CD123 binding domain.

Abstract: The invention provides compositions and methods for treating diseases associated with expression of CD20 or CD22. The invention also relates to chimeric antigen receptor (CAR) specific to CD20 or CD22, vectors encoding the same, and recombinant T or natural killer (NK) cells comprising the CD20 CAR or CD22 CAR. The invention also includes methods of administering a genetically modified T cell or NK cell expressing a CAR that comprises a CD20 or CD22 binding domain.

Abstract: The invention provides compositions and methods for treating diseases associated with expression of CD20 or CD22. The invention also relates to chimeric antigen receptor (CAR) specific to CD20 or CD22, vectors encoding the same, and recombinant T or natural killer (NK) cells comprising the CD20 CAR or CD22 CAR. The invention also includes methods of administering a genetically modified T cell or NK cell expressing a CAR that comprises a CD20 or CD22 binding domain.