TAC T-Cell Therapy vs CAR T-Cell Therapy

Triumvira Immunologics believes they are developing the next step up from chimeric antigen receptor (CAR) T-cells in cancer care with their T-cell antigen coupler (TAC) technology, which is designed to activate T-cell receptors (TCRs) through more natural pathways than CAR T-cells.

The company’s lead program, TAC-01 HER 2, initiated a phase 1/2 trial (NCT04727151) in April 2021, while TAC-02 HER2, the allogeneic version of the TAC T-cell therapy, is in investigational new drug (IND)-enabling studies. A BCMA-targeted therapy for multiple myeloma is also in IND-enabling studies.

GeneTherapyLive spoke with Paul Lammers, MD, MSc, president and chief executive officer, Triumvira Immunologics, to learn more about the TAC technology and its potential in both hematologic malignancies and solid tumors.

GeneTherapyLive: Tell us about Triumvira and your differentiated approach to cell therapies.

Paul Lammers, MD, MSc: We are developing a set of unique and targeted T-cell therapeutics, both autologous and allogeneic, that are totally different than other current, especially CAR T-cell receptor technologies. We believe our TAC technology is the next step forward in cell therapy. So, we have a huge opportunity here to build a strong pipeline.

What are the advantages of TAC technology over standard CAR-T and TCR-based therapies?

So, initially, our founder Jonathan Bramson, PhD, and a post-doc in his lab, Christopher Helsen, PhD, who is now our director of platform development, set out to work on T-cell activation, and of course, initially did a lot of work on CAR T-cells, which at that time was an up-and-coming technology. They found the CAR Ts to be very effective, but they killed so many animals, it was ridiculous. So toxicities are a huge challenge. 

Right now, if you look at our 3 market products targeting CD19, they all have the same Blackbox warning because of the toxicities associated. So, they wanted to find a more natural way of activating the T-cell than with a synthetic receptor like a CAR. They started looking at different ways of doing that, developing different constructs and landed on the TAC technology, which they developed and found to be extremely effective and extremely safe in in-vivo models. So, that's really the technology on which the company was based.

Can you talk about the TAC-01 HER2 candidate?

So, we have an opportunity to pursue both solid as well as liquid, or hematological malignancies, whether it be CD19 or BCMA. The solid tumor program is our biggest opportunity because CAR Ts have a tough time in solid tumors. CAR T-cells are either on or very on, there’s no off-switch. The cell is always activated, even when you don't want it to be. During manufacturing, you already start producing cytokines because that's how they're built. These cells run out of juice, they produce so many cytokines, and they don’t really have the persistence and fitness that you need in order to create an effective cell therapy product for solid tumors. In hematological malignancies, the tumor cells are right in your blood system or in your lymph system, it's very easy to get to. In solid tumors on peripheral tissues, it's a totally different animal, it's much more difficult to get there. 

HER2 is a well-known target in solid tumors and there are quite a few products approved for breast and gastric cancers that overexpress HER2. However, there are many other tumors that overexpress HER2 for which there are no available therapies yet. Even within breast and gastric cancers, there is still a high unmet need for patients that develop resistance to initial targeted therapies. So, we decided to target HER2 with TAC-01 HER2, which is a single administration of a potentially curative therapy that is very appealing to oncologists and patients who have already been through chemo, through HERceptins, and other products.

Where is TAC-01 HER2 at in terms of clinical development?

We just started a clinical trial. We have MD Anderson and Dana Farber as our first 2 sites that are open and starting to screen and enroll patients. We’ll add another 4 sites in the next weeks and months. We're getting well-experienced cell therapy principal investigators that are very excited to get involved. Everybody wants to get their hands on the TAC T cell. We will update the community throughout conferences and provide updates on the progress of the study, and we're very excited.

What other candidates are in the pipeline?

So, we’ve seen phenomenal data in preclinical models with TAC cells in other targets aside from HER2. We did an exhaustive bioinformatics analysis last year looking at promising new targets in solid tumors, we identified 9 to 10 and added 3 to our pipeline. There’s ET42, Gucci2C, and GPC3. All 3 are expressed in major tumors, whether that be lung or gastric or colon cancer. So, we truly have an opportunity to make an impact in solid tumors.

Transcript edited for clarity.