TCX-102 Program








TCX-102: AML mutNPM1
TCX-102: AML mutNPM1


BlueSphere’s TCX-102 program is an autologous, engineered TCR T-cell therapy. This program builds upon the TCX-101 program by targeting an additional subset of patients with AML that have mutations in a gene called nucleophosmin-1 (NPM1).

Our lead candidate TCR candidate for this program has been identified and is currently in IND-enabling studies.

How does a T cell therapy work?
  • T cells kill targeted cells by using their TCR to identify fragments of antigens (peptides) presented by Human Leukocyte Antigens (HLA) molecules expressed by target cells. Think of this as a ‘lock and key’ system. 
  • The TCR on the T cells acts as the key and the HLA-peptide on the target cell acts as the lock. If a T cell ‘key’ finds the right ‘lock’, it destroys the cell. 
  • T cells can be engineered to have specific keys. When given to patients that have cancerous cells with a corresponding lock, then the TCR T cell therapy works to kill those cancerous cells.
  • Nucleophosmin (NPM1) is a gene that is mutated in about 30% of AML patients. Mutant NPM1 is a driver mutation, meaning it is responsible for starting and sustaining leukemia. 
  • NPM1 is also a founder mutation, meaning it is present in all leukemia cells of a patient, making it an ideal target.
  • The mutations in NPM1 result in a change in the amino acid sequence, e., they generate neoantigens.

NPM1 mutation is present in:

of all AML patients
of patients with normal cytogenetics
  • Fragments of the mutated NPM1 protein are expressed on the HLA molecules of AML-specific cells and can act as ‘lock’s for specific T cell ‘keys’ to target and kill.
  • TCX-102 is an engineered TCR T-cell therapy that recognizes and kills mutant NPM1-expressing cells.
  • Since mutated NPM1 is only present in leukemia cells, T cells that target the mutation will only kill leukemia cells and not harm the normal blood cells or blood cell precursors.
  • This cell therapy product is autologous, meaning it takes the patient’s own T cells, modifies them to be specific for targeting mutant NPM1, and reintroduces them into the patient where they then search for and kill the mutant NPM1-expressing cancerous cells. It is not given in combination with allogeneic stem cell transplant.

Together, TCX-101 and TCX-102 create a best-in-class portfolio for high-risk leukemia patients that address multiple critical points in AML disease progression to have a high impact on survival.

Contact us to hear more about our clinical programs and technology.