Improving Immunizations by Suppressing Autophagy in Cells (UCLA Case No. 2023-291)

UCLA researchers in the Department of Molecular, Cell and Developmental Biology have developed methods to suppress autophagy in cells to enhance immune response. These methods target local tumor sites instead of the whole body, thus reducing off-target effects and are applicable to a variety of cancer types, including solid and hematological tumors.

BACKGROUND: Activating the immune response is a promising way to help the body’s natural defense mechanisms recognize and destroy cancer cells. While targeted therapies and immune checkpoint inhibitors can be effective, they benefit only a limited number of patients, can lead to resistance, and in many cases cause serious side effects. Allogeneic hematopoietic stem cell transplantation is another method to activate the immune response, but its effectiveness for solid tumors is limited due to the risk of graft-versus-host disease. Autologous chimeric antigen receptor (CAR)-T cell therapy eliminates the risk of graft-versus-host disease, but it also faces limitations in treating solid tumors due to poor accumulation at the tumor site. An ideal approach would involve activating an anti-tumor immune response that is specific to the tumor site, rather than systemwide.

INNOVATION: UCLA researchers have developed methods that enhance the immune response by suppressing autophagy in antigen-presenting immune cells. They discovered that inactivating autophagy in the entire mouse or in bone marrow-derived cells resulted in reduced melanoma growth. Elevated inflammatory gene expression and an increase in immune cells were observed in autophagy-deficient mice with melanoma. When combining autophagy inhibition with immune checkpoint blockade, the melanomas were smaller than with either treatment alone. By disrupting the autophagy pathway in immune-related cells and loading them with tumor or other antigens, this approach can effectively activate the patient’s immune response, which in turn reduces tumor growth.

POTENTIAL APPLICATIONS:

  • Enhancing immune response
  • Treatment of cancer and infectious diseases

ADVANTAGES:

  • Triggers a localized anti-tumor immune response at the tumor site, instead of a systemic response, thereby reducing side effects
  • Applicable to various cancer types, including solid and hematological tumors

DEVELOPMENT-TO-DATE: Successful demonstration of the method in autophagy-deficient mice in melanoma model.

KEYWORDS: Immunization, immune activation, immunotherapy, cancer, autophagy-deficient, dendritic cell, antigen, tumor, immune response, autophagy pathway

Patent Information: