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EP-4736852-A2 - METHODS AND COMPOSITIONS FOR TREATING CANCER AND INFECTIOUS DISEASES

EP4736852A2EP 4736852 A2EP4736852 A2EP 4736852A2EP-4736852-A2

Abstract

The invention relates to compositions comprising a CD4 lymphocyte depleting agent; and methods of using the compositions to treat, prevent, reduce the severity of and/or slow the progression of a condition in a subject. The invention also relates to use of combinations of a CD4 lymphocyte depleting agent and at least one additional agent to treat, prevent, reduce the severity of and/or slow the progression of a condition in a subject. The additional agent may be an immune check point inhibitor, an adoptive immune therapeutic, an immune adjuvant, or an immune modulating agent, or their combinations.

Inventors

  • KIM, HYUNG
  • WANG, YANPING

Assignees

  • Cedars-Sinai Medical Center

Dates

Publication Date
20260506
Application Date
20150205

Claims (10)

  1. A CD4 lymphocyte depleting agent for use in a method of treating, reducing the severity of and/or slowing the progression of breast cancer, colon cancer, renal cancer or a combination thereof in a subject, wherein: (a) the CD4 lymphocyte depleting agent is to be administered in combination with an immune check point inhibitor; (b) the CD4 lymphocyte depleting agent is an anti-CD4 antibody; and (c) the immune checkpoint inhibitor is an anti-PD-1 antibody or an antigen-binding fragment thereof, wherein the subject is human.
  2. A immune checkpoint inhibitor for use in a method of treating, reducing the severity of and/or slowing the progression of breast cancer, colon cancer, renal cancer or a combination thereof in a subject, wherein: (a) the immune checkpoint inhibitor is to be administered in combination with a CD4 lymphocyte depleting agent; (b) the CD4 lymphocyte depleting agent is an anti-CD4 antibody; and (c) the checkpoint inhibitor is an anti-PD-1 antibody or an antigen-binding fragment thereof, wherein the subject is human.
  3. A combination for use in treating, reducing the severity of and/or slowing the progression of breast cancer, colon cancer, renal cancer or a combination thereof in a subject, the combination comprising: (a) a CD4 lymphocyte depleting agent, wherein the CD4 lymphocyte depleting agent is an anti-CD4 antibody; and (b) an immune check point inhibitor, wherein the immune checkpoint inhibitor is an anti-PD-1 antibody or antigen-binding fragment thereof, wherein the subject is human.
  4. The CD4 lymphocyte depleting agent, the immune checkpoint inhibitor, or the combination for use according to any one of claims 1 to 3, wherein the anti-CD4 antibody is selected from the group consisting of a monoclonal antibody, a chimeric antibody, a humanized antibody, a human antibody, and a single chain antibody.
  5. The CD4 lymphocyte depleting agent, the immune checkpoint inhibitor, or the combination for use according to claim 4, wherein the CD4 lymphocyte depleting agent is a humanized anti-CD4 antibody.
  6. The CD4 lymphocyte depleting agent, the immune checkpoint inhibitor, or the combination for use according to claim 5, wherein the CD4 lymphocyte depleting agent is zanolimumab.
  7. The CD4 lymphocyte depleting agent, the immune checkpoint inhibitor, or the combination for use according to any of the preceding claims, wherein the anti-PD-1 antibody or antigen-binding fragment thereof, is selected from the group consisting of a monoclonal antibody or antigen-binding fragment thereof, a chimeric antibody, a humanized antibody, a human antibody or antigen-binding fragment thereof, and a single chain antibody.
  8. The CD4 lymphocyte depleting agent, the immune checkpoint inhibitor, or the combination for use according to claim 7, wherein the anti-PD-1 antigen-binding fragment is selected from a Fab, a F(ab')2, or an Fv fragment.
  9. The CD4 lymphocyte depleting agent, the immune checkpoint inhibitor, or the combination for use according to any preceding claim, wherein the CD4 lymphocyte depleting agent, the immune checkpoint inhibitor, or the combination are for intravenous, intraperitoneal, intramuscular or subcutaneous administration.
  10. The CD4 lymphocyte depleting agent, the immune checkpoint inhibitor, or the combination for use according to any preceding claim, wherein the CD4 lymphocyte depleting agent and the immune checkpoint inhibitor are administered sequentially, wherein the CD4 lymphocyte depleting agent is administered before the immune checkpoint inhibitor.

Description

FIELD OF THE INVENTION The present invention relates to molecular immunology and cell biology. Specifically described herein are compositions and methods for treating cancer or infectious diseases using CD4 lymphocyte depleting agents alone or in a combination with any one or more of an immune check point inhibitor, an adoptive immune therapeutic, an immune adjuvant, or an immune modulating agent. BACKGROUND All publications cited herein are incorporated by reference in their entirety to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference. The following description includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the presently claimed invention, or that any publication specifically or implicitly referenced is prior art. The immune system can provide protection against cancers. Effective immune stimulation produces long-lasting memory lymphocytes, capable of rapidly responding to repeat antigen challenge. CD4 expressing lymphocytes include both helper T cells and regulatory T cells. T helper cells are critical to mounting an adoptive immune response. However, regulatory T cells (Tregs) inhibit the function of cytotoxic T cells and normally function to limit an immune response. Therefore, CD4 depletion was evaluated as a strategy for removing Treg activity. Although only a small fraction of CD4 lymphocytes are Treg cells, CD4 depletion remains an effective approach for depleting Treg activity, and importantly, it has the potential for rapid translation to clinical use. Humanized CD4 depleting antibodies have been evaluated as a strategy to inhibit the immune system in clinical trials for autoimmune disorder. However, described herein is the use of CD4 lymphocyte depleting antibody to stimulate the immune system. Provided herein are therapies against cancer and infectious diseases in subjects by combining depletion of CD4+ lymphocytes with any one or more of an immune check point inhibitor, an adoptive immune therapeutic, an immune adjuvant, and an immune modulating agent, or a combination thereof. SUMMARY OF THE INVENTION Various embodiments of the present invention provide methods for treating, preventing, reducing the severity of and/or slowing the progression of a condition in a subject. The method includes providing a composition comprising a CD4 lymphocyte depleting agent and administering a therapeutically effective amount of the composition to the subject, thereby treating, preventing, reducing the severity of and/or slowing the progression of the condition in the subject. Various embodiments of the present invention provide methods for treating, preventing, reducing the severity of and/or slowing the progression of a condition in a subject. The method includes providing a CD4 lymphocyte depleting agent and at least one additional agent selected from the group consisting of an immune check point inhibitor, an adoptive immune therapeutic, an immune adjuvant, and an immune modulating agent; and administering a therapeutically effective amount of the CD4 lymphocyte depleting agent and a therapeutically effective amount of the at least one of an immune check point inhibitor, an adoptive immune therapeutic, an immune adjuvant, and an immune modulating agent to the subject, thereby treating, preventing, reducing the severity of and/or slowing the progression of the condition in the subject. In some embodiments, the methods further comprise administering a therapeutically effective amount of mTOR inhibitor. Various embodiments of the present invention provide methods for treating, preventing, reducing the severity of and/or slowing the progression of a condition in a subject. The methods include providing a CD4 lymphocyte depleting agent and an adoptive immune therapeutic agent (for example, a dendritic cell (DC) vaccine) and administering a therapeutically effective amount of the CD4 lymphocyte depleting agent and a therapeutically effective amount of the adoptive immune therapeutic agent thereby treating, preventing, reducing the severity of and/or slowing the progression of the condition in the subject. Various embodiments of the present invention provide methods for treating, preventing, reducing the severity of and/or slowing the progression of a condition in a subject. The methods include providing a CD4 lymphocyte depleting agent and a checkpoint inhibitor (for example, an anti-PD-1 antibody) and administering a therapeutically effective amount of the CD4 lymphocyte depleting agent and a therapeutically effective amount of the checkpoint inhibitor thereby treating, preventing, reducing the severity of and/or slowing the progression of the condition in the subject. Various embodiments of the present invention provide methods for treating, preventing, reducing the severity of and/or slo