TT12 (HPVST) is an investigational cell therapy being developed by Tessa Therapeutics as a potential treatment for patients with cervical and oropharyngeal cancer.

How TT12 works

Cervical and oropharyngeal cancer are strongly associated with human papillomavirus (HPV) infection. TT12 comprises a preparation of cytotoxic (or cell-killing) T-cells extracted from the blood of patients with HPV-positive cancer. These cells are then cultured and expanded in the laboratory. Cytotoxic T-cells are a subset of specialized T-cells that have the ability to detect and kill abnormal or diseased cells in the body.

To make these T-cells more active and induce a stronger immune response, TT12 is engineered to be resistant to transforming growth factor beta (TGF-β), a protein produced by HPV cancers that inhibits T-cell activation and expansion.

Upon expansion, the engineered cytotoxic T-cells are infused back into the patients’ body where they target HPV-positive cells and initiate a specific immune response leading to tumor cell death and inhibition of tumor growth.

TT12 in clinical trials

TT12 was first evaluated in a study involving 68 HPV-associated cancer patients. The results of the study, published in the Journal of Immunotherapy, showed that TT12 generated a cytotoxic response against viral antigens (proteins) called E6 and E7, which are responsible for the development of the cancer. 

Based on this finding, TT12 is being investigated in a Phase 1 clinical trial (NCT02379520) called the HESTIA study designed to treat patients with relapsed HPV-associated cancers. The main goals of the study are to investigate the safest dose, clinical outcome, side effects, and length of time TT12 lasts in the body of the patients. The trial is recruiting up to 32 participants at Houston Methodist Hospital, Texas.

If the treatment with TT12 cells alone proves to be safe, an additional group of patients will be treated with a combination therapy of TT12 plus Opdivo in a lymphodepleted environment, meaning that the patients have fewer lymphocytes in circulation.

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Inês Martins holds a BSc in Cell and Molecular Biology from Universidade Nova de Lisboa and is currently finishing her PhD in Biomedical Sciences at Universidade de Lisboa. Her work has been focused on blood vessels and their role in both hematopoiesis and cancer development.
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Inês Martins holds a BSc in Cell and Molecular Biology from Universidade Nova de Lisboa and is currently finishing her PhD in Biomedical Sciences at Universidade de Lisboa. Her work has been focused on blood vessels and their role in both hematopoiesis and cancer development.