Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Mini Oral session: Haematological malignancies

621MO - Preclinical study of DASH CAR-T cells manufactured in 48 hours

Date

12 Sep 2022

Session

Mini Oral session: Haematological malignancies

Topics

Cell-Based Therapy;  Immunotherapy

Tumour Site

Haematological Malignancies

Presenters

Haiying Wang

Citation

Annals of Oncology (2022) 33 (suppl_7): S283-S294. 10.1016/annonc/annonc1055

Authors

H. Wang, S. Tsao, Q. Xiong, M. Gu, C. Fu, X. Li, M. Zhang, N. Li, H. Hu

Author affiliations

  • Department Of Research And Development, Hrain Biotechnology Co., Ltd., 201210 - Shanghai/CN

Resources

Login to get immediate access to this content.

If you do not have an ESMO account, please create one for free.

Abstract 621MO

Background

Patients with acute lymphoblastic leukemia (ALL) or relapsed/refractory (r/r) large B-cell lymphoma (LBCL) often progress rapidly, and current manufacture process of chimeric antigen receptor (CAR) T cells takes too long and resulting products are less optimal for in vivo expansion and function. The “DASH CAR-T” manufacturing process we developed enabled production of CAR-T cells of naïve phenotypes within 48 hours. We examined the efficacy of DASH CAR-T cells in a murine model and laid the foundation for novel clinical trials for patients with ALL or r/r B-ALL.

Methods

DASH CAR-T process consisted of 24-hour T-cell activation and subsequent 24-hour transduction with a gamma-retrovirus vector encoding a second generation anti-CD19 CAR. The cell surface marker expression and in vitro function were accessed by flow cytometry analysis. NOG (NOD/Shi-scid/IL-2Rγnull) mouse (n=5) mice bearing Nalm6-luciferase lymphoma were treated with a graded number of control T cells that activated but not transduced (1×106) or transduced with anti-BCMA conventional CAR (1×106), anti-CD19 conventional CAR-T cells (1or 5×106), or anti-CD19 DASH CAR-T cells (1×106). Human CD45+ T cells in peripheral blood (PB) was determined by flow cytometry. Tumor burden was imaged using in vitro imaging system and survival of mice were recorded.

Results

DASH CAR-T cells were mainly “naïve” T cells (CD45RO-/CCR7+). Adoptive transfer of 1×106 DASH CAR-T cells showed an extensive expansion (increased 156 fold) in vivo at day 21, whereas 5×106 conventional CAR-T cells actually contracted (decreased 77 fold) in mice. This extraordinary CAR-T expansion led to a significantly better therapeutic effect and prolonged survival. Untreated mice, mice treated with control T cells, or 4 out of 5 mice treated with anti-BCMA CAR were dead at day 28 after cell infusion. Strikingly, 4 out 5 mice treated with one million anti-CD19 DASH CAR-T cells survived beyond 60 days. In contrast, 1 or 2 out of 5 mice treated with one million or 5 million anti-CD19 CAR-T cells survived.

Conclusions

DASH CAR-T cells manufactured in two days expanded significantly better in vivo and more effective than conventional CAR-T cells. Clinical trials are planned to use DASH CAR-T platform to rapidly generate CAR-T cells to treat patients with ALL or r/r B-ALL.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Hrain Biotechnology Co., Ltd.

Funding

Hrain Biotechnology Co., Ltd.

Disclosure

H. Wang: Financial Interests, Personal, Full or part-time Employment: Hrain Biotechnology Co., Ltd. S. Tsao: Financial Interests, Personal, Full or part-time Employment: Hrain Biotechnology Co., Ltd. Q. Xiong: Financial Interests, Personal, Full or part-time Employment: Hrain Biotechnology Co., Ltd. M. Gu: Financial Interests, Personal, Full or part-time Employment: Hrain Biotechnology Co., Ltd. C. Fu: Financial Interests, Personal, Full or part-time Employment: Hrain Biotechnology Co., Ltd. X. Li: Financial Interests, Personal, Full or part-time Employment: Hrain Biotechnology Co., Ltd. M. Zhang: Financial Interests, Personal, Full or part-time Employment: Hrain Biotechnology Co., Ltd. N. Li: Financial Interests, Personal, Full or part-time Employment: Hrain Biotechnology Co., Ltd. H. Hu: Financial Interests, Personal, Full or part-time Employment: Hrain Biotechnology Co., Ltd.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.