AbbVie and Xilio Partner Up to Advance Tumor-Activated T Cell Engagers

BiTEs Take Center Stage

Bispecific T cell engagers (BiTEs) have risen to prominence due to their success against hematologic malignancies. These antibodies work by binding to T cells via CD3 while simultaneously targeting a strategic tumor-associated antigen (something like CD20, CD19, or BCMA), facilitating the engagement of T cells to cancer cells. As of now, eight FDA-approved T cell engagers are available, with seven targeting B cell malignancies such as ALL and multiple myeloma, and only one against solid tumors (Immunocore’s IMMTAX for uveal melanoma).

However, despite their success, the widespread utility of BiTEs is hindered due to the risk of severe toxicities – mainly cytokine release syndrome (CRS), a potentially life-threatening immune overactivation. This, along with the lack of tumor-associated antigens has made it difficult for T cell engagers to gain traction in solid tumor indications.

Can Xilio’s Tumor-Activated Technology Unlock BiTEs Full Therapeutic Potential?

Xilio’s tumor-activated technology offers a potential solution. Their platform incorporates a masking domain that keeps the engager inactive until it encounters matrix metalloproteases (MMPs) in the tumor microenvironment. MMPs are highly active within tumors but largely absent in healthy tissues, enabling precise activation of the therapy where it’s needed most. This approach minimizes off-target effects and promises to improve tolerability – an absolute game-changer for T cell engagers in solid tumors.

AbbVie’s Strategic Focus on T Cell Engagers

AbbVie’s partnership with Xilio is not its first foray into T cell engager technology – it’s actually their third major deal in recent months. Back in October 2024, AbbVie collaborated with EvolveImmune Therapeutics on a CD3- and CD2-targeting multispecific antibody designed to enhance T cell co-stimulation for both solid and hematologic cancers. This was followed by a January 2025 agreement with Simcere Zaiming for a trispecific antibody for multiple myeloma.

The company has already demonstrated success with its BCMA-targeting bispecific antibody ABBV-383 for multiple myeloma and continues to build its portfolio through strategic partnerships. By teaming up with Xilio, AbbVie is really leaning in to its ambition to overcome the toxicity and efficacy barriers that have limited the use of T cell engagers in solid tumors.

This partnership also reinforces broader trends in oncology, where innovation is increasingly focused on overcoming the challenges posed by the tumor microenvironment. With tumor-activated therapeutics gaining momentum, we may be on the cusp of a breakthrough year for immunotherapy – especially for solid tumors.