During the last decade, a revived enthusiasm about T-cell related therapies emerged after promising clinical outcomes. Nevertheless, many patients (especially with solid tumours) still do not have adequate therapeutic options. The complexity of the tumour microenvironment is a likely factor acting in detriment of many of those therapies by multiple suppressive mechanisms. To tackle a complex mechanism, an oncolytic adenovirus 2 (Ad5/3-E2F-d24-hTNFa-IRES-hIL2, a.k.a. TILT-123) was engineered to enable T-cell therapies in those circumstances.
To study the efficacy of TILT-123 together with different T-cell related therapies (adoptive cell transfer, checkpoint inhibitors and CAR T cell therapy) different models were used including mouse, Syrian Hamster and patient derived in vivo models for different indications were tested.
Antitumor efficacy analyses showed complete responses in all animals receiving a T-cell therapy or checkpoint inihibitor (aPD1 or aPDL-1) and the T-cell enabling virus. Further, other aspects such as safety, influence on different immune populations, abscopal effect, antitumor memory and ability to replace lympho-depleting chemotherapy and postconditioning with high-dose IL-2 treatment were studied.
The use of TILT-123 to enable T-cell therapies (including checkpoint-inhibiting antibodies) delivered encouraging preclinical results pointing to it as a valuable approach to increase the number of patients that benefit from T-cell therapies. Those results include not only cell based therapies but also checkpoint inhibitors, a kind of therapy that is making the difference in the field and becoming first-line treatment for an increasing number of indications. Because of the favourable preclinical studies, the first in human clinical trials with TILT-123 will start in the upcoming months.
The authors.
TILT Biotherapeutics.
V. Cervera-Carrascon: Full / Part-time employment: TILT Biotherapeutics. R. Havunen: Full / Part-time employment: TILT Biotherapeutics. J.M. Santos: Full / Part-time employment: TILT Biotherapeutics. A. Hemminki: Shareholder / Stockholder / Stock options, Full / Part-time employment, Officer / Board of Directors: TILT Biotherapeutics. All other authors have declared no conflicts of interest.