CD19 specific CAR T cell therapy

Autologous T cells engineered to express a CD19-specific chimeric antigen receptor (CAR) mediate high rates of complete response (CR) in patients with B-cell malignancies...Patients were enrolled on 3 dose levels (DLs): 1×107 (DL 1), 3×107 (DL 2), or 1×108 (DL 3) CAR-NKT cells/m2, given after lymphodepleting conditioning with cyclophosphamide and fludarabine...In conclusion, initial results from our first-in-human clinical evaluation of allogeneic CAR-NKTs indicate that these cells are well tolerated and can mediate objective responses in relapsed or refractory NHL and ALL patients even at low doses. Thus, CAR-NKTs represent a promising platform for "off-the-shelf" cancer immunotherapy.

P1, N=48, Recruiting, Baylor College of Medicine | Trial primary completion date: Apr 2023 --> Apr 2024

P1, N=64, Recruiting, Baylor College of Medicine | Trial completion date: Feb 2034 --> Feb 2036 | Trial primary completion date: Dec 2022 --> Dec 2024

P1, N=64, Recruiting, Baylor College of Medicine | Trial completion date: Feb 2033 --> Feb 2034 | Trial primary completion date: Dec 2021 --> Dec 2022

Commercial tisagenlecleucel in CAYA RR B-ALL demonstrates efficacy and tolerability. This first analysis of commercial tisagenlecleucel stratified by disease burden identifies HB preinfusion to associate with inferior OS and EFS and increased toxicity.

Autologous T cells engineered to express a CD19-specific chimeric antigen receptor (CAR) mediate high rates of complete response (CR) in patients with B-cell malignancies...Pts received 1×10 7 (DL 1) or 3×10 7 (DL 2) CAR-NKT cells/m 2 following lymphodepleting conditioning with cyclophosphamide and fludarabine...In conclusion, our data indicate that allogeneic CAR-NKT cells are well-tolerated and can mediate objective responses in relapsed/refractory NHL and ALL pts even at the low doses tested. Our initial results from this first-in-human clinical evaluation of allogeneic CAR-NKTs suggest that NKTs represent a promising platform for “off-the-shelf” cancer immunotherapy.

Adoptive transfer of CD19-specific chimeric antigen receptor T-cells (CAR-T cells) has transformed the treatment paradigm of relapsed/refractory (R/R) CD19 B-cell malignancies, dramatically improving remission rates and cures in patients with chemo-refractory disease. However, the applicability of CD19 CAR-T cells is limited to B cell malignancies and antigen loss can result in treatment failure, prompting the exploration of alternative targets to overcome tumor escape via CD19 antigen loss, as well as extend the CAR-T cell platform to treat Hodgkin and T cell lymphomas. This review highlights recent clinical trials testing CAR-T cell targets beyond CD19.

Autologous T cells engineered to express a CD19-specific chimeric antigen receptor (CAR) mediate high rates of complete response (CR) in patients with B-cell malignancies...Patients received 10 7 (DL 1) or 3×10 7 (DL 2) CAR-NKT cells per square meter of body surface area following lymphodepleting conditioning with cyclophosphamide/fludarabine...In conclusion, our data indicate that allogeneic CAR-NKT cells are well-tolerated and can mediate objective responses in relapsed/refractory NHL and ALL patients even at the low doses tested. Our initial results from this first-in-human clinical evaluation of allogeneic CAR-NKTs suggest that NKTs represent a promising platform for “off-the-shelf” cancer immunotherapy.

We performed a Phase I clinical trial of donor derived CD19-specific chimeric antigen receptor T-cells (CAR T-cells) for B-cell malignancy that relapsed or persisted after matched related allogeneic hemopoietic stem cell transplant...Although CAR T-cells have an enviable record of safety to date, our results emphasize the need for caution and regular follow up of CAR T recipients, especially when novel methods of gene transfer are used to create genetically modified immune therapies. The trial was registered at www.anzctr.org.au as ACTRN12617001579381.

P1, N=64, Recruiting, Baylor College of Medicine | Trial primary completion date: Dec 2020 --> Dec 2021

P1, N=48, Recruiting, Baylor College of Medicine | N=20 --> 48

P1, N=64, Recruiting, Baylor College of Medicine | Trial primary completion date: Dec 2019 --> Dec 2020