Nova Patents
EP3552628A1

Vista modulators for diagnosis and treatment of cancer

Abstract

The present disclosure relates to compositions and therapeutic methods for activating an immune response in a patient in need thereof. In a preferred embodiment, the subject methods and compositions are able to antagonize the activity of VISTA, a naturally occurring "checkpoint" protein which contributes to immune tolerance, optionally in combination with an antagonist of a second checkpoint pathway such as PD-1. For example, such methods and compositions may be suitable for preventing and treating colon cancer or another cancer. An exemplary VISTA antagonist, specifically, an anti-VISTA antibody, is demonstrated herein to activate an immune response against cancer cells in vitro and in vivo, thereby conferring protective anti-tumor immunity which decreased tumor burden. Additionally, an additive benefit was observed when a VISTA antagonist was used in combination with a second checkpoint protein antagonist, specifically, an antibody against PD-1 ligand (PD-L1).

EP3552628A1, drawing sheet 1
Sheet 1 of 95

Term

Projected expiry 9 September 2033.

  1. Priority
  2. Filed
  3. Published
  4. Today
  5. Projected expiry

13 claims: 3 independent, 10 dependent

  1. 1
    A VISTA antagonist for use in treating cancer by activating anti-cancer immunity in a subject, wherein the VISTA antagonist comprises an anti-VISTA antibody, and wherein said use further comprises administering a PD-1 antagonist to the subject, wherein the PD-1 antagonist is selected from an anti-PD-1 antibody, an anti-PD-L1 antibody, an siRNA targeting expression of PD-1, an siRNA targeting the expression of PD-L1, or a peptide, fragment, dominant negative form, or soluble form of PD-1 or PD-L1.
  2. 4
    A VISTA antagonist and a PD-1 antagonist for use in combination in treating a subject having a cancer or infectious condition that would benefit from upregulation of an immune response, wherein said VISTA antagonist comprises an anti-VISTA antibody, which when administered is capable of inhibiting the VISTA-mediated suppression of immune responses, and wherein said PD-1 antagonist is selected from an anti-PD-1 antibody, an anti-PD-L1 antibody, an siRNA targeting expression of PD-1, an siRNA targeting the expression of PD-L1, or a peptide, fragment, dominant negative form, or soluble form of PD-1 or PD-L1.
  3. 6
    The VISTA antagonist for use according to any one of claims 1 to 3, wherein the cancer is colorectal cancer, sarcoma, melanoma, lymphoma, leukemia, neuroblastoma or carcinoma.
  4. 8
    A therapeutic composition for use in the treatment of cancer, wherein said therapeutic composition comprises a VISTA antagonist and a PD-1 antagonist;wherein said VISTA antagonist comprises an anti-VISTA antibody and said PD-1 antagonist is an anti-PD-L1 antibody, an anti-PD-1 antibody, an siRNA targeting expression of PD-1, an siRNA targeting the expression of PD-L1, or a peptide, fragment, dominant negative form, or soluble form of PD-1 or PD-L1.
  5. 11
    The therapeutic composition for use according to any one of claims 8 to 10, wherein the composition is for use in a cancer therapeutic regimen, which is effected in combination with another anti-cancer treatment, optionally radiotherapy, chemotherapy, and/or administration of an anti-cancer biologic, thereby increasing the efficacy of said other anti-cancer treatment.
  6. 12
    The therapeutic composition for use according to any one of claims 8 to 11, which when administered is capable of synergistically inhibiting cancer cell growth as compared to compositions comprising anti-VISTA antibodies alone and said PD-1 antagonist alone.
  7. 13
    The therapeutic composition for use according to any one of claims 8 to 11, wherein the composition is to be used in a subject having cancer at the site of said cancer or into a blood vessel that supplies blood to said cancer.
Independent claims7