Joining the immunotherapy revolution: Adoptive cell therapy against cancer

Project Details

diagrammatic depiction showing elimination of lymphoma

Lymphoma cells are eliminated following adoptive transfer of lymphoma antigen-specific cytotoxic CD8+ T cells.
Mice bearing control Eμ-myc-GFP or Eμ-myc-GFP-OVA lymphoma (arrows) were injected with/without exogenously generated anti-OVA cytotoxic CD8+ T cells 3 days after lymphoma inoculation. Two days later, tumour load in the spleen of mice was analysed by FACS.

During cancer development, tumour cells generate neo-antigens on their surface, which can be recognized as foreign by cytotoxic CD8+ T lymphocytes (CTL). Following recognition of the tumour-associated antigens, tumour cells are targeted for elimination. A current cancer therapy in the clinic involves manufacture of tumour-specific CTL capable of destroying specifically tumour cells, and injection of the CTL into patients. While this revolutionary therapy shows great promise, impairment of the CTL in many patients prevents its full potential to be realised. To overcome these limitations, we are characterising the mechanisms that cause anti-cancer CTL inactivation.

Researchers

Professor Jose Villadangos

Collaborators

Professor William Heath, Peter Doherty Institute

Dr Justine Mintern, Bioi21

Research Publications

Prato S, Mintern JD, Lahoud MH, Huang DC, Villadangos JA.  Induction of antigen-specific effector-phase tolerance following vaccination against a previously ignored B-cell lymphoma. Immunol Cell Biol 2011; 89: 595-603.

Prato S, Zhan Y, Mintern JD, Villadangos JA. Rapid deletion and inactivation of CTLs upon recognition of a number of target cells over a critical threshold. J Immunol 2013; 191: 3534-3544.

Segal G, Prato S, Zehn D, Mintern JD, Villadangos JA.  Target density, not affinity or avidity of antigen recognition, determines adoptive T cell therapy outcomes in a mouse lymphoma model. J Immunol 2016; In Press

Villadangos JA. Antigen-specific impairment of adoptive cell therapy against cancer: players, mechanisms, solutions and a hypothesis. Immunol Rev 2016; 272:169-182.

Research Group

Villadangos laboratory: Antigen presenting cells & molecules that initiate T cell immunity against pathogens and cancer



Faculty Research Themes

Infection and Immunology

School Research Themes

Infection & Immunity, Therapeutics & Translation



Key Contact

For further information about this research, please contact the research group leader.

Department / Centre

Microbiology and Immunology