Alaunos Therapeutics’ Early data Shows Promising Feasibility

Sleeping Beauty TCR-T cells in Phase I/II study

Alaunos’ Clinical TCR Library targets the most frequent mutations in KRAS, TP53, and EGFR which are prevalent in gastrointestinal (colon, bile duct, pancreas), lung, and gynecological (ovary and endometrial) cancers in a number of different HLA alleles. Therefore, our TCR-T cell Library approach has the potential to benefit a significant population of patients with unmet clinical needs.

The non-viral Sleeping Beauty transposon/transposase system is used to introduce the TCR gene into autologous T cells from the patient. Sleeping Beauty transposition is cost-effective, rapid, flexible, and efficiently integrates the introduced TCR for stable, long-term expression. 

The TCR-T Library Phase I/II trial is an open-label, dose-escalation trial being conducted at MD Anderson. The trial is actively enrolling patients with NSCLC, colorectal, endometrial, pancreatic, and ovarian, and bile duct cancers that have a matching human leukocyte antigen (HLA) whose tumors contain at least one of the targeted driver mutations in KRAS, TP53, and EGFR.

Data from three adult patients who have been treated with Sleeping Beauty TCR-T cells in Phase I/II study (NCT05194735) were presented in a poster session at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting. The study’s primary objective for the Phase I portion was to define the incidence of dose-limiting toxicities (DLTs) and the maximum tolerated dose or recommended Phase II dose to be explored in disease-specific cohorts during Phase II.

In three treated patients the first was a 34-year-old female with Stage IV mucinous adenocarcinoma NSCLC refractory to chemotherapy and immunotherapy who received DL1 (0.9 x 1010 TCR-T cells) targeting KRASG12D and HLA-A*11:01, the second was a 54-year-old female with stage IVA chemotherapy-resistant colorectal cancer who received DL2 (6.4 x 1010 TCR-T cells) targeting p53R175H and HLA-A*02:01 and the third was a 60-year-old male with stage IV pancreatic cancer refractory to chemotherapy who received DL2 (5.8 x 1010 TCR-T cells) targeting KRASG12V and HLA-A*11:01.

Overall a manageable safety profile with no unexpected adverse events, DLTs, or immune effector cell-associated neurotoxicity syndrome (ICANS) was observed. Patients 1, 2, and 3 had cytokine release syndrome Grades 2, 3, and 1, respectively that were self-limiting or resolved with standard management and anti-IL-6 antibody in the case of Patient 2. The best overall responses were partial response for Patient 1 with six months of progression-free survival, a stable disease for Patient 2, and progressive disease for Patient 3. The persistence of TCR-T cells was observed in all patients at the last follow-up and out to 6 months in the case of Patient 1.

KOL insights

“TCR-T cell therapy has shown early promise as a potential cancer treatment. There remains a significant unmet medical need for new, patient-specific therapies for people living with difficult-to-treat solid tumor cancers. These early data are encouraging as they showed an objective clinical response and persistence alongside a favorable safety and tolerability profile in patients who have not responded to prior lines of therapy.”–Expert Opinion.


TCR-T cells demonstrate the feasibility of redirected T cell targeting of driver mutations in solid tumors. The sleeping Beauty transposon/transposase system is an effective platform for the manufacture of a TCR-T cell library. The Infusion products of the first three patients treated on this study were all 290% transgenic mTCR. Following the infusion TCR-T cells exhibit persistence and tumor infiltration as in peripheral blood, TCR-T cells could be detected in all patients at the last evaluable time point and were detected out to 7 months post-infusion. In two patients with on-treatment biopsies collected at week 7 (Pt-03) and month 6 (Pt-01), TCR-T cells could be detected and isolated from ex vivo expanded tumor-infiltrating lymphocytes (TIL).

In the first-in-human study of Sleeping Beauty TCR-T cells, encouraging signs of efficacy, safety, and persistence of the TCR-T cells were observed. This innovative treatment holds promise for patients diagnosed with solid tumors that express shared mutations in driver genes such as KRAS and TP53. The preliminary findings suggest that this therapy has the potential to effectively target and address the underlying genetic abnormalities driving the growth of these tumors. Further research and larger-scale trials are warranted to validate these promising early results and assess the long-term benefits for patients