Cornell University

Immune Disease Institute, Inc.

Affyimmune Therapeutics, Inc.

Moonsoo Jin

Timothy Alan Springer

Janusz Puc

Huan Yang

The present invention relates to chimeric antigen receptors (CARs) specific to ICAM-1 comprising I domain of the αsubunit 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 μM 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.

I domain chimeric antigen receptor specific to ICAM-1

The present invention is directed to transduced T cells expressing at least 100,000 molecules of human somatostatin receptor 2 (SSTR2), which improves PET/CT imaging sensitivity. The present invention is also directed to transduced T cells expressing SSTR2 and chimeric antigen receptor (CAR). In one embodiment, the CAR is specific to human ICAM-1 and the CAR comprises a binding domain that is scFv of anti-human ICAM-1, or an I domain of the αL subunit of human lymphocyte function-associated antigen-1. In another embodiment, the CAR is specific to human CD19, and the CAR comprises a binding domain that is scFv of anti-human CD19. The present invention is further directed to using the above transduced T cells for monitoring T cell distribution in a patient by PET/CT imaging and/or treating cancer.

Transduced T cells expressing human SSTR2 and application thereof

The present invention provides EpCAM antibodies with different affinities. The present invention also provides chimeric antigen receptors (CARs) specific to EpCAM. CAR T cells comprising human EpCAM scFv having a low and sufficient affinity to EpCAM can avoid targeting healthy tissues with low EpCAM expression while exhibiting long-term efficacy against tumor tissues with high EpCAM expression. The present invention also relates to an adoptive cell therapy method for treating cancer by administering the CAR-T cells comprising human EpCAM scFv to a subject suffering from cancer, whereby the CAR T cells bind to the cancer cells overexpressing EpCAM and kill the cancer cells.

EpCAM antibody and CAR-T cells

The present invention is directed to transduced T cells expressing at least 100,000 molecules of human somatostatin receptor 2 (SSTR2), which improves PET/CT imaging sensitivity. The present invention is also directed to transduced T cells expressing SSTR2 and chimeric antigen receptor (CAR). In one embodiment, the CAR is specific to human ICAM-1 and the CAR comprises a binding domain that is scFv of anti-human ICAM-1, or an I domain of the &#x3b1;L subunit of human lymphocyte function-associated antigen-1. In another embodiment, the CAR is specific to human CD19, and the CAR comprises a binding domain that is scFv of anti-human CD19. The present invention is further directed to using the above transduced T cells for monitoring T cell distribution in a patient by PET/CT imaging and/or treating cancer.

The present invention relates to chimeric antigen receptors (CARs) specific to ICAM-1 comprising I domain of the &#x3b1;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 &#x3bc;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 present invention provides an isolated polypeptide capable of binding toCAM-1, comprising the integrin (XL I domain or biologically active portion thereof, wherein one or more residues is substituted, wherein the substituted polypeptide binds ICAM-I at a higher affinity than wild type integrin CCL protein. The invention provides a method for inhibiting ICAM-I and a pharmaceutical composition comprising an integrin (XL I domain polypeptide or biologically active portion of the polypeptides. The invention also provides a method of treating or preventing an LFA-I mediated ICAM-1 associated disease such as inflammation, artherosclerosis, allograft rejection, diabetes, T-cell mediated sensitization reaction, psoriasis, HIV infection, or rheumatoid arthritis.

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New York, NY, United States of America

Moonsoo Jin