Periodic Reporting for period 1 - ITHACA (Immuno-targeting of human AML quiescent cells by a novel phage display approach.)
Periodo di rendicontazione: 2018-01-01 al 2019-06-30
Therapies allowing the recognition of human tumor cells by the immune system (immunotherapies) have revolutionized cancer treatment for an enormous number of patients. However, the creation of robust immunotherapies has remained frustratingly limited, leaving most tumors treatable by only chemotherapeutic or radiological regimens. Immunotherapies primarily consist of antibodies which are created against antigens that are expressed exclusively- or predominantly- by tumor cells, and the limited applicability of immunotherapies is a direct result of the difficulty of discovering these tumor-associated antigens. Therefore, methods that allow for the creation and validation of antibodies that can target and kill tumors specifically, regardless of the targeted antigen, may be one way to address this clinical need.
We have set up an innovative method which enables the isolation of antibodies manifesting high specificity for human tumor cells in vivo without prior knowledge on the antigen. In so doing we can validate candidates to select for those most capable of mounting a robust anti-tumor response for human tumors currently lacking an immunotherapeutic option.
Using our proprietary platform, we have selected a group of antibodies that are predicted to exhibit strong binding-specificity for human Acute Myeolid Leukemias (AMLs), a hematological cancer which remains extremely lethal due, in part, to the inability to develop efficacious immunotherapies targeting the disease. In particular, we have chosen to create antibodies specifically targeting the AML tumor “brains:” the rare subset of tumor stem cells that allow for the growth of human AMLs and their eventual relapse post-chemotherapy. We have successfully isolated a cohort of candidate antibodies predicted to bind human AMLs, and we are in the process of validating their tumor-specificity and in vivo anti-tumor efficacy.
Our initial findings with different human tumor models have drawn the interest of companies in exploiting the methodology we have implemented to address the treatment of heretofore untreatable human tumors. The intellectual property related to the project outcomes has been secured by filing a patent application aimed at covering the unique and innovative antibody-screening platform already developed in-house. Discussions are ongoing with potential industrial partners to exploit the potential of our platform by strategic partnership.
The socioeconomic repercussions of our findings are potentially enormous, as the potential to improve patients’ prognosis and reduce the burden for the healthcare system. Human AMLs remain one of the most pernicious tumors, with a 5-year survival rate in adult cases of only 20-25%, representing approximately 2% of the world-wide cancer-associated deaths. Therefore, an immunotherapeutic approach to confront the disease could have profound implications for hundreds of thousands of patients every year.
We have set up an innovative method which enables the isolation of antibodies manifesting high specificity for human tumor cells in vivo without prior knowledge on the antigen. In so doing we can validate candidates to select for those most capable of mounting a robust anti-tumor response for human tumors currently lacking an immunotherapeutic option.
Using our proprietary platform, we have selected a group of antibodies that are predicted to exhibit strong binding-specificity for human Acute Myeolid Leukemias (AMLs), a hematological cancer which remains extremely lethal due, in part, to the inability to develop efficacious immunotherapies targeting the disease. In particular, we have chosen to create antibodies specifically targeting the AML tumor “brains:” the rare subset of tumor stem cells that allow for the growth of human AMLs and their eventual relapse post-chemotherapy. We have successfully isolated a cohort of candidate antibodies predicted to bind human AMLs, and we are in the process of validating their tumor-specificity and in vivo anti-tumor efficacy.
Our initial findings with different human tumor models have drawn the interest of companies in exploiting the methodology we have implemented to address the treatment of heretofore untreatable human tumors. The intellectual property related to the project outcomes has been secured by filing a patent application aimed at covering the unique and innovative antibody-screening platform already developed in-house. Discussions are ongoing with potential industrial partners to exploit the potential of our platform by strategic partnership.
The socioeconomic repercussions of our findings are potentially enormous, as the potential to improve patients’ prognosis and reduce the burden for the healthcare system. Human AMLs remain one of the most pernicious tumors, with a 5-year survival rate in adult cases of only 20-25%, representing approximately 2% of the world-wide cancer-associated deaths. Therefore, an immunotherapeutic approach to confront the disease could have profound implications for hundreds of thousands of patients every year.