Provided are an anti-CD7 nanobody and a derivative thereof. The derivative comprises a humanized anti-CD7 nanobody, a chimeric antigen receptor based on a single nanobody, a chimeric antigen receptor based on a double nanobody, a recombinant expression vector, an engineered host cell, a conjugate, a pharmaceutical composition, a kit, and a reagent for detecting CD7 on the cell surface. The nanobody has a good affinity to CD7, and the prepared CAR-T cells target and recognize tumor antigens and have high killing activities against tumor cells.

Compositions and methods for depleting B cells and/or eliminating neutralizing antibodies, particularly for AA V gene therapy administration, are disclosed. Neutralizing alloantibodies (NAbs) to adeno-associated virus (AAV) occur both naturally after exposure to the wildtype circulating virus and following AAV vector mediated gene therapies. When pre-existing, these NAbs preclude eligibility to receive curative AAV gene therapy vectors. Following AAV infusion, the development of NAbs preclude re-administration even with other vector serotypes due to cross-reactivity. Given waning of transgene activity seen in multiple AAV gene therapy trials for hemophilia and the potential need to boost responses with growth in pediatric patients, the ability to re-administer AAV vectors is critical.

Provided herein are D domain containing polypeptides that specifically bind targets of interest, as are nucleic acids encoding the D domain containing polypeptides, vectors containing the nucleic acids and host cells containing the nucleic acids and vectors. Also provided herein are methods of making and using the D domain containing polypeptides, nucleic acids, vectors and host cells, for example, but not limited to, in diagnostic and therapeutic applications. Also provided herein are multi-functional chimeric antigen receptor (CAR)-based compositions and Adapters and their use in methods of directing immune responses to target cells. In some embodiments, the methods include the use of a CAR expressing cell in combination with an Adapter. The Adapter confers the ability to modulate, alter, and/or direct CAR expressing cell-mediated immune response in vitro and in vivo.

The present disclosure provides tumor neoantigenic peptide sequences and nucleotide sequences encoding such peptide sequences; a vaccine or immunogenic composition capable of raising a specific T-cell response comprising one or more of the neoantigenic peptides, or comprising nucleic acid encoding one or more of the neoantigenic peptides; an antibody, or an antigen-binding fragment thereof, a T cell receptor (TCR), or a chimeric antigen receptor (CAR) that specifically binds such neoantigenic peptides; methods of producing such antibodies, TCRs or CARs; polynucleotides encoding such neoantigenic peptides, antibodies, CARs or TCRs, optionally linked to a heterologous regulatory control sequence; immune cells that specifically bind to such neoantigenic peptides; and dendritic cells or antigen presenting cells that have been pulsed with one or more of the neoantigenic peptides; and methods of using such products in particular therapeutic uses of these products.

The invention is directed to a bispecific chimeric antigen receptor, comprising: (a) at least two antigen-specific targeting regions; (b) an extracellular spacer domain; (c) a transmembrane domain; (d) at least one co-stimulatory domain; and (e) an intracellular signaling domain, wherein each antigen-specific targeting region comprises an antigen-specific single chain Fv (scFv) fragment, and binds a different antigen, and wherein the bispecific chimeric antigen receptor is co-expressed with a therapeutic control. The invention also provides methods and uses of the bispecific chimeric antigen receptors.

The present invention refers to a bispecific in tandem receptor CAR, named RfuCAR, which includes a scFv that recognizes and ligates surface molecules on tumoral cells (CD33, CD123 or another tumoral target) and the IL-1 receptor type 2 (IL-1R2). According to this, the IL1-R2 was chosen as the ideal receptor to compose the RfuCAR construction, being able to capture the IL-1 with high affinity and specificity. These proprieties indicate it as a good candidate to reduce the neurotoxicity and CRS effects of CAR-T therapies. Additionally, the present invention deals with a method for modulating the tumoral microenvironment, for example, in case of acute myeloid leukemia, or other cancer type like but not restricted to acute lymbloblastic leukemia, pancreatic, lung and ovarian cancer.

The present invention relates to engineered cells expressing a fusion protein comprising a peptide fusion inhibitor and a CXCR4 protein that lacks signaling activity. Also provided are methods of suppressing, inhibiting, preventing or treating a HIV infection in a subject in need thereof using the engineered cells.

Disclosed herein are recombinant antibodies specific to programmed death 1 (PD-1), chimeric antigen receptors (CARs) and genetically modified cells configured to express the CARs on their surfaces and secret the recombinant antibodies specific to PD-1. Also disclosed herein is a method of treating cancer by administering the genetically modified cells to a subject afflicted with cancer.

The present invention relates to a humanized anti-CD28 antibody, a multispecific antibody comprising the humanized anti-CD28 antibody, especially a bispecific antibody comprising the humanized anti-CD28 antibody and an anti-CD40 antibody, a polynucleotide encoding these antibodies, a vector comprising the polynucleotide, a host cell comprising the polynucleotide or the vector, and a pharmaceutical composition comprising same. The present invention also relates to use of the humanized anti-CD28 antibody in inducing T cell proliferation and use of the bispecific antibody in enhancing the killing effect of immune cells on a target cell.

Disclosed are compositions and methods for targeted treatment of SSTR-expressing cancers. For example, disclosed herein are Bispecific T-Cell Engaging (BiTE) molecules (fusion polypeptides) (also referred to herein as bispecific molecules) that are able to crosslink CD3 complex on immune effector cells with SSTR2 on NETs. Also disclosed are chimeric antigen receptor (CAR) polypeptides that can be used with adoptive cell transfer to target and kill SSTR-expressing cancers. Also disclosed are immune effector cells, such as T cells or Natural Killer (NK) cells, that are engineered to express these CARs. Therefore, also disclosed are methods of providing an anti-tumor immunity in a subject with a SSTR-expressing cancer, such as a neuroendocrine tumor, that involves adoptive transfer of the disclosed immune effector cells engineered to express the disclosed CARs.