The present invention relates to chimeric antigen receptors (CARs) specific to ICAM-1 comprising I domain of the .sub.L subunit of human lymphocyte function-associated antigen 1 (LFA-1). The invention particularly relates to CARs comprising human I domains having different affinities (1 mM to 1 nM Kd) to ICAM-1. CAR T cells comprising human I domain having a low affinity (1 to 200 M Kd) to ICAM-1 can avoid targeting healthy tissues with basal ICAM-1 expression while simultaneously exhibiting increased potency and long-term efficacy against tumor tissues with high ICAM-1 expression. The present invention also relates to an adoptive cell therapy method for treating cancer by administering the CAR-T cells comprising human I domain to a subject suffering from cancer, whereby the CAR T cells bind to the cancer cells overexpressing ICAM-1 and kill the cancer cells.

The disclosure describes T cells that express chimeric antigen receptors (CARs), as well as pharmaceutical compositions comprising T cells and methods of making and using such T cells. Particularly, this disclosure describes T cells expressing a CAR that binds to CD64, and methods of use in treating acute myeloid leukemia.

Disclosed herein are antibodies and antigen binding fragments thereof that specifically bind human CD4. Also disclosed are fusion proteins comprising a glycoprotein G of the Paramyxoviridae family and CD4 antibodies for targeting and transducing cells expressing CD4. Viral vectors and other compositions containing the fusion proteins, as well as methods of using the fusion proteins, are also disclosed.

The present invention relates to a P2Y purinoceptor 2 (P2RY2) activity modulator for use in T cell immunotherapy. The present invention further relates to a polynucleotide encoding a P2RY2 activity modulator and to a host cell comprising the P2RY2 activity modulator for use in T cell immunotherapy. Furthermore, the present invention relates to a method of identifying 5 a subject amenable to T cell immunotherapy comprising (A) determining in a sample of said subject the activity of P2RY2; (B) comparing the activity determined in step (A) to a reference; and identifying a subject amenable to T cell immunotherapy based on the comparison of step (B), as well as to a method for identifying a P2RY2 activity modulator, said method comprising (I) contacting a host cell with a candidate compound suspected to be a P2RY2 activity 10 modulator; (II) determining B7-H3 activity in said host cell; (III) comparing the B7-H3 activity determined in step (II) to a control; and (IV) identifying a P2RY2 activity modulator based on the comparison in step (III).

Disclosed is a chimeric antigen receptor (CAR) against programmed death ligand 1 (PD-L1) and application thereof. In particular, the CAR comprises an antigen-binding domain which binds to PD-L1; and the anti-PD-L1 CAR-T cells thus produced are useful in CAR cell therapy.

The present invention relates to a chimeric antigen receptor (CAR) against programmed death ligand 1 (PD-L1) and application thereof. In particular, the CAR comprises an antigen-binding domain which binds to PD-L1; and the anti-PD-L1 CAR cells thus produced are useful in CAR cell therapy.

The present invention relates to FcRH5 binding domains. In particular, the invention provides single domain antibodies, antibody conjugates, chimeric antigen receptors (CARs) and immune cell engagers which comprise such binding domains.

The present disclosure relates to cell therapy methods for treating solid carcinoma tumors comprising administration of immune cells expressing a chimeric antigen receptor (CAR) comprising a mutant I domain of the .sub.L subunit of human lymphocyte function-associated antigen-1 (LFA-1), which are cytotoxic against solid carcinoma tumors overexpressing ICAM-1 and alleviate on-target, off-tumor toxicities.

Embodiments disclosed herein provide compositions for enhancing anti-tumor immunity for treating cancer by targeting the polyamine pathway, and in particular inhibiting the function of the polyamine catabolic enzyme Sat1. In embodiments, Sat1 inhibition is targeted to CD4+ T cells, in particular Tregs.

The present invention relates to a hybrid treatment of a tumor/cancer, said treatment comprises (i) targeting the resolution of transcription-replication conflicts in a tumor/cancer; or (ii) inducing in a tumor/cancer; and the use/administration of an immune cell, or a progenitor cell thereof, which is resistant against/less susceptible to said targeting/inducing. The immune cell, or progenitor cell thereof, is envisaged to target a/said (cell(s) of) a/said (solid) tumor/cancer. The present invention further relates to a respective immune cell, or a progenitor cell thereof. The present invention further relates to a pharmaceutical composition comprising the immune cell and/or a progenitor cell thereof and to a pharmaceutical composition, a kit or a combination (e.g. set of two/three components) comprising the immune cell and/or a progenitor cell thereof and a DDIA. The present invention further relates to methods of screening for a target of a DDIA which is resistant against/less susceptible to said DDIA or for an agent that is capable of inhibiting a target in a cell of a cancer/tumor and thereby inducing DNA damage and/or preventing resolution of DNA damage in said cell of a cancer/tumor; and that is incapable of inhibiting said target which is resistant against/less susceptible to said agent in an immune cell, or progenitor cell thereof, and thereby not inducing DNA damage and/or not preventing resolution of DNA damage in said immune cell or progenitor cell thereof.