The present disclosure provides methods and compositions for genetically modifying lymphocytes, for example T cells and/or NK cells. In some embodiments, the methods include reaction mixtures, and resulting cell formulations, that are created using whole blood, or a component thereof that is not a PBMC, and additionally comprise T cells and recombinant retroviral particles having polynucleotides that encode a CAR. In some embodiments, modified lymphocytes are reintroduced into a subject subcutaneously. In some embodiments, polynucleotides that provide T cells the ability to regulate cell survival and proliferation in response to binding to a CAR, are provided.

Provided herein are antibodies and antigen-binding portions thereof that bind to tumor endothelial marker 1 (TEM1), as well as methods of using the disclosed antibodies and antigen-binding portions thereof, including methods of treating cancer, reducing tumor growth, reducing tumor metastasis, and/or reducing tumor-associated fibrosis in a subject in need thereof.

Described herein are antigen binding proteins with specificity to Melanoma-Associated Antigen A4 (MAGE-A4) peptide-MHC (pMHC). Also described are multispecific antigen binding proteins comprising an antigen binding domain with specificity to CD3, and at least one MAGE-A4 pMHC antigen binding domain. Methods of treating cancer with the same are also described.

Circular RNA, along with related compositions and methods are described herein. In some embodiments, the inventive circular RNA comprises group I intron fragments, spacers, an IRES, duplex forming regions, and an expression sequence. In some embodiments, the expression sequence encodes an antigen. In some embodiments, circular RNA of the invention has improved expression, functional stability, immunogenicity, ease of manufacturing, and/or half-life when compared to linear RNA. In some embodiments, inventive methods and constructs result in improved circularization efficiency, splicing efficiency, and/or purity when compared to existing RNA circularization approaches.

The present invention relates to a novel chimeric antigen receptor comprising a CD99 region which participates in immune synapse stabilization as a backbone of the chimeric antigen receptor, an immune cell comprising the same, and the uses thereof. CD99-based CAR-T cells are capable of forming very stable immune synapses with tumor cells compared to conventional backbone-based CAR-T cells and can exhibit improved tumor therapeutic efficiency, so they can be useful for immune cell therapy for the treatment of cancer.

The presently disclosed subject matter provides for antigen-recognizing receptors that specifically target CD33 and cells comprising such CD33-targeted antigen-recognizing receptors. The presently disclosed subject matter further provides uses of the CD33-targeted antigen-recognizing receptors for treatment.

Provided herein are a recombinant chimeric antigen receptor (CAR) fusion protein, a method of modifying an immune cell into a CAR immune cell by treating the immune cell with the recombinant CAR fusion protein, and a method of treating cancer by administering the CAR immune cell to a subject in need thereof.

Provided are B cell-activating factor receptor (BAFF-R)-binding molecules, in particular, to human antibodies specific for BAFF-R, including antibody fragments. The present disclosure further relates to recombinant receptors, including chimeric antigen receptors (CARs) that contain such antibodies or fragments, and polynucleotides that encode the antibodies, antigen-binding fragments or receptors specific for BAFF-R. Also provided are CARs which contain extracellular binding domains that bind to BAFF-R and B-lymphocyte antigen CD19 (CD19), genetically engineered cells expressing such CARs, and uses thereof in adoptive cell therapy.

In certain aspects, provided herein are compositions and methods for treating cancer. The methods of the present disclosure comprise administering to a subject in need thereof a NK cell expressing a CAR in combination with an antigen-binding molecule that binds to a tumor antigen, wherein the CAR-NK cell targets tumor cells through binding to the antigen-binding molecule.

Provided herein are Chimeric Antigen Receptor (CAR) polypeptides, polynucleotides encoding the CARs, host cells containing or expressing the CARs and polynucleotides and methods of use to treat viral infections such as COVID or cancers in patients in need thereof.