Embodiments of the disclosure concern methods and compositions for delivering therapeutic, diagnostic or interventional moieties, such as complex and simple entities such as biologies, including at least cells, for example. The methods employ targeted delivery by employing at least one ALCAM-binding moiety on the therapeutic, diagnostic or interventional moiety to be delivered. In specific cases, the ALCAM-binding moiety is present on or with the therapeutic moiety in multiple iterations. In certain embodiments, the ALCAM-binding moiety comprises at least one SRCR domain from CD6 and a stalk, such as from CD6, of the secretable or molecular form thereof.

The present invention generally relates to T-cells, such as CD8+ T-cells, CD4+ T-cells, CD3+ T-cells, T-cells or natural killer (NK) T-cells, transfected/transduced with a fusion protein which is recruited by the use of trivalent, bispecific antibody molecule which specifically binds to/interacts with the extracellular domain of the fusion protein. More precisely, the present invention relates to a kit comprising the nucleic acid molecules, vectors and/or the fusion proteins of the present invention and the trivalent, bispecific antibody molecules of the present invention. Further aspects of the inventions are expression vectors comprising nucleic acid molecules encoding the fusion proteins as well as the trivalent, bispecific antibody molecules. Further, a process for the production of the trivalent, bispecific antibody molecules of the invention and a medicament/pharmaceutical composition comprising said trivalent, bispecific antibody molecules are described. The invention also provides the use of said trivalent, bispecific antibody molecules in a method for the treatment of particular diseases as well as a pharmaceutical compositions/medicament comprising said trivalent, bispecific antibody molecules, wherein said trivalent, bispecific antibody molecule(s) is (are) to be administered in combination with transduced T-cells comprising the fusion protein of the invention. The invention also provides a method for the treatment of particular diseases.

The present invention relates to the use of interleukin-15 (IL-15) as selectable marker for gene transfer, preferably of at least one gene of therapeutic interest, into a mammalian cell or cell line, in particular a human cell or cell line. The present invention furthermore relates to transgenic mammalian cells or cell lines expressing IL-15 as selectable marker and co-expressing at least one protein of interest encoded by at least one gene of interest, which is preferably a protein of therapeutic interest. The present invention is in particular suitable for chimeric antigen receptors (CARs) as the gene or protein of interest and their expression in lymphocytes. The transgenic mammalian cells and cell lines are furthermore suitable for use as a medicament, in particular in the treatment of cancer and in immunotherapy, such as adoptive, target-cell specific immunotherapy.

The invention is based upon the discovery that T regulatory type 1 (Tr1) cells express particular cell surface markers that allow for their selection, enrichment, isolation, purification and administration. The ability to use the particular markers described herein to select, enrich, isolate, purify and administer Tr1 cells allows for improved methods of Tr1 therapies for treating a wide variety of diseases and disorders.

The invention relates to chimeric antigen receptor (CAR) specific to p80 and CD146, vectors encoding the same, and recombinant T cells comprising the p80 or CD146 CAR. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises a p80 or CD146 binding domain.

The invention provides improved T cell compositions and methods for manufacturing T cells. More particularly, the invention provides methods of T cell manufacturing that result in adoptive T cell immunotherapies with improved survival, expansion, and persistence in vivo.

Provided herein are acute myeloid leukemia antigen targets for chimeric receptors and methods of using same.

An isolated antigen-binding protein may be capable of binding to CLDN18.2. Such an isolated antigen-binding protein may include HCDR1, HCDR2, and/or HCDR3. The HCDR1 may include an amino acid sequence as set forth in any one of SEQ ID NO: 2, SEQ ID NO: 10, and SEQ ID NO: 16. The HCDR2 may include an amino acid sequence as set forth in SEQ ID NO: 68 or SEQ ID NO: 11. The HCDR3 may include an amino acid sequence as set forth in SEQ ID NO: 67. A chimeric antigen receptor may include the isolated antigen binding protein. A method may make such an antigen-binding protein and an antigen binding protein and the chimeric antigen receptor may be derived from the isolated antigen-binding protein.

The present disclosure generally relates to, among other things, a new class of receptors engineered to modulate transcriptional regulation in a ligand-dependent manner. In particular, the new receptors contain a heterologous stop-transfer-sequence and a ?-secretase cleavable transmembrane domain. The disclosure also provides compositions and methods useful for producing such receptors, nucleic acids encoding same, host cells genetically modified with the nucleic acids, as well as methods for modulating an activity of a cell and/or for the treatment of various diseases such as cancers.

A cancer treatment composition and a cancer treatment method. Provided are a cancer treatment method and a treatment composition for patients for whom an anti-PD-1 antibody or anti-PD-L1 antibody treatment has failed.