Engineered Cell Therapies

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We aim to re-invent engineered cell therapies to broaden the universe of patients benefiting from the powerful potential

The tailored reprogramming of autologous T cells from cancer patients to recognize and attack their tumors has become a disruptive medical innovation. Retargeting of T cells can be achieved via introduction of tumor-specific receptors into patient-derived T cells. For that purpose, T cells are mostly engineered to express either T cell receptors, or TCRs, or chimeric antigen receptors, or CARs. Recently, CAR expressing T cells, or CAR T cells, became the first engineered T cell therapy to obtain FDA approval for some B cell derived hematological malignancies.

While CAR T therapy has shown potent anti-tumor responses in patients with B cell malignancies, clinical efficacy in solid tumors so far is limited. The main hurdles for application of CAR T therapies in solid tumors are:

  • Lack of highly tumor selective targets, which are needed for safe and effective tumor targeting
  • Low anti-tumoral activity due to insufficient expansion of engineered T cells

We are developing the next generation of engineered T cell therapies that:

  • Target novel and known tumor-specific antigens, including mutant neoantigens, and a broad spectrum of tumor-associated antigens expressed in a wide range of cancers
  • Leverage our proprietary FixVac technology for controlled and safe in vivo stimulation, activation and expansion of engineered T cells

Our innovative approach to CAR T therapy development – in vivo CAR T expansion

Engineered Cell Therapies

Besides targeting an ideal tumor-specific antigen, the frequency and the persistence of CAR T cells in the respective patient is a critical factor determining antitumor efficacy. To address this critical factor, we developed an approach for in vivo stimulation of CAR T cells that relies on our proprietary FixVac technology for systemic mRNA delivery in combination with our CAR T product candidates.

Intravenous administration of a FixVac, encoding for the tumor antigen, induces expression of the desired target on antigen-presenting cells in secondary lymphoid tissues. FixVac treatment facilitates in vivo expansion of CAR T cells in a dose-dependent manner. Moreover, repeated administration of FixVac results in an improved CAR T cell persistence as well as an increased anti-tumor efficacy.

Our TCR discovery and validation platform will tackle key challenges

We have developed an integrated technology platform for the systematic identification of functional, fully human TCRs from single antigen-reactive T cells. This technology consists of a proprietary high-throughput approach for the fast retrieval, cloning and rapid validation of novel paired T cell receptor sequences. Our approach facilitates the isolation of tumor cell-specific TCRs against multiple antigens and various Human Leukocyte Antigen (HLA) class I and II alleles.

We believe our TCR discovery technology has the potential to unlock an array of patient and tumor specific TCRs suitable for clinical use. We believe this technology has potential utility for:

  • Therapeutic TCR products encompassing single TCRs for targeting a specific antigen
  • A therapeutic TCR warehouse encompassing multiple TCRs for targeting of one or more tumor antigens
  • Individualized T cell therapy involving on-demand identification and timely manufacturing of customized, engineered T cells with autologous TCRs against neoepitopes for adoptive transfer.

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