The present disclosure describes compositions and methods for treating cancers such as acute myeloid leukemia (AML), in particular relapsed and refractory AML. The method entails administering to the patient an antibody or a chimeric antigen receptor (CAR)-expressing immune cell targeting a molecule such as CD33, CD123, CD117 or CLL-1 following, or concurrently with, transplanting to the patient an engineered stem cell expressing the same molecule but with a mutation disrupting the epitope to the antibody or CAR. Due to the mutation, the engineered stem cell, unlike endogenous hematopoietic cells, is not targeted by the therapy and thus can supply the patient with functional hematopoietic cells and antigens.

Disclosed are proteins with antibody heavy chain and light chain variable domains that can be paired to form an antigen-binding site targeting BAFF-R on a cell, pharmaceutical compositions comprising such proteins, and therapeutic methods using such proteins and pharmaceutical compositions, including for the treatment of cancer or autoimmune disease.

Provided herein are multispecific proteins and compositions (e.g., pharmaceutical compositions) comprising the same; as well as methods of making the multispecific proteins and compositions. The multispecific proteins provided herein are useful in pharmaceutical compositions and methods, including, e.g., methods of treating diseases (e.g., cancer), methods of activating T-cells, and methods of inducing or enhancing an immune response.

The present invention provides a cell-based platform for controllable, regionalized, and cost-effective delivery of immunomodulator and other therapeutic proteins, which is widely applicable in cancer immunotherapy.

The present disclosure relates to promoter constructs comprising: one or more heat shock elements: a core promoter; and a gene of interest: vectors comprising the promoter constructs, and immune cells modified to include the promoter constructs. The promoter constructs provide the ability to remotely control immune cell therapies by thermal targeting. The present disclosure also provides methods of use for the promoter constructs.

The present invention relates to methods for developing engineered immune cells such as T-cells for immunotherapy that have a higher potential of persistence and/or engraftment in host organism. IN particular, this method involves an inactivation of at least one gene involved in self/non self recognition, combined with a step of contact with at least one non-endogenous immunosuppressive polypeptide. The invention allows the possibility for a standard and affordable adoptive immunotherapy, whereby the risk of GvH is reduced.

Embodiments of the disclosure include methods and compositions in which NK cells are modified by the hand of man to express the T-cell receptor and CD3 co-receptor on NK cells that do not naturally express them. Such modified NK cells work effectively with bispecific or multi-specific antibodies that are tailored to comprise anti-CD3 antibodies that bind the modified NK cells, thereby triggering signaling, activation, and cytotoxicity of target cells to which the antibodies also bind. Thus, the NK cells are specifically configured to be able to work effectively with Bispecific NK cell engagers (BiKEs) as well as Bispecific T cell Engagers (BiTEs).

The present invention relates to compositions and methods for enhancing T cell metabolism and activity for more effective adoptive T cell therapy. By expressing an chimeric antigen receptor and bispecific antibodies in T cells, the T cells are metabolically enhanced with improved cytotoxicity and resistance to immunosuppression imposed by tumor microenvironments. Certain aspects include modified T cells and pharmaceutical compositions comprising the modified cells for adoptive cell therapy and treating a disease or condition associated with enhanced immunity.

The present invention relates to compositions and methods for enhancing T cell metabolism and activity for more effective adoptive T cell therapy. By expressing an chimeric antigen receptor and bispecific antibodies in T cells, the T cells are metabolically enhanced with improved cytotoxicity and resistance to immunosuppression imposed by tumor microenvironments. Certain aspects include modified T cells and pharmaceutical compositions comprising the modified cells for adoptive cell therapy and treating a disease or condition associated with enhanced immunity.

The invention provides therapeutic humanized anti-HERV-K antibodies, CAR, or a fusion thereof consisting of a bispecific T cell engager (BiTE) FOR CD3 and CDS, a DNA-encoded BiTE (DBiTE), or an antibody-drug conjugate (ADC). The invention also relates to peptides, proteins, nucleic acids, and cells for use in immunotherapeutic methods. In particular, the invention relates to the immunotherapy of cancer peptides bound to molecules of the MHC, or peptides as such, which can also be targets of antibodies and other binding molecules.