Nature's universal CAR-T announces preclinical data targeting two hematological malignancies

May 1, 2022/eMedClub News/--Recently, Cellectis published two articles in the journal Nature about its general-purpose CAR-T product candidate, UCART123
.

The published article presents preclinical data of UCART123 in the treatment of AML (acute myeloid leukemia) and BPDCN (cystic plasmacytoid dendritic cell tumor), showing strong in vitro and in vivo activity of UCART123, and is a promising candidate for allogeneic CAR-T The efficacy of cell therapy in AML (acute myeloid leukemia) provides preclinical proof of concept
.

▲ Image source: Celletis' official website UCART123 is a CAR transgenic allogeneic T cell that targets CD123.
CD123 is a leukemia cell mainly expressed on AML and BPDCN (cystic plasmacytoid dendritic cell tumor).
antigen
.

Recommended reading: UCART123 clinical trial ushered in the first rare leukemia patient, universal CAR-T therapy will shine in the field of hematological malignanciesYimai Meng revealed that AML is a bone marrow malignancy originating from leukemia stem cells (LSC).
It occurs from genetic mutations in hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) and is characterized by rapid growth of abnormal cells that accumulate in the bone marrow and blood and interfere with normal blood cell production
.

The disease progresses rapidly and is one of the most aggressive and difficult blood cancers to treat, with extremely low patient survival rates
.

Recommended reading: The 2021 American Society of Hematology (ASH) annual meeting is about to open.
What are the new developments in the treatment of acute myeloid leukemia (AML) this year? Yimai Meng broke the news that preclinical research led by Dr.
Monica Guzman showed that UCART123 demonstrated cytotoxic activity against primary AML samples, with minimal toxicity to normal hematopoietic progenitor cells; targeting AML cells in vivo, improving patient-derived Overall survival in a sex xenograft (PDX) model; in a competitive mouse model with primary AML and normal myeloid cells, primary AML cells can be selectively depleted without affecting hematopoiesis
.

▲ The process of the mouse experiment, picture source: Nature communications At the same time, the published preclinical data also showed that UCART123 effectively eliminated AML without significant impact on normal hematopoietic progenitor cells; it proved that UCART123 has strong anti-BPDCN activity; Human evaluation for the treatment of r/r AML (adult relapsed or refractory acute myeloid leukemia) is also currently in Phase 1 clinical trials of the AMELI-01 study
.

▲ UCART123, image source: Celletis official website BPDCN (cystic plasmacytoid dendritic cell tumor) is a highly aggressive hematological cancer, which is mainly caused by the overexpression of interleukin-3 receptor subunit α (IL3RA or CD123) transformed plasmacytoid dendritic cells
.

The morphology of BPDCN tumor cells is variable, and it is indistinguishable from lymphoma cells and primitive monocytes only in terms of morphology, which can easily lead to misdiagnosis, often with skin lesions as the first symptom, which can simultaneously involve bone marrow, lymph nodes, other soft tissues and the central nervous system, etc.
, is more common in the elderly, more men than women, and has a poor prognosis, and the effect is not good under conventional treatment
.

Recommended reading: ASH heavy: City of Hope announces CD123 CAR-T clinical results, the first BPDCN patient achieved complete remission Antitumor activity, the differential expression of CD123 on the surface of BPCDN cells makes it an attractive therapeutic target, preclinical results using in vitro and in vivo analysis of primary BPDCN samples show that UCART123 cells have in vitro specific killing of BPDCN primary samples , and impacted in vivo xenograft (PDX) experiments; eradicated BPDCN and achieved long-term disease-free survival in a primary patient-derived BPDCN xenograft mouse model; and observed CD123 deletion in one of the established PDX models resulting in evasion of UCART123 treatment and consequent early relapse
.

▲ Image source: Nature communications researchers also evaluated the potential of allogeneically edited CAR-T cells to eliminate LSC (UCART123) against CD123 in this study
.

"While the few CD123 T cell therapies evaluated to date have mostly relied on autologous approaches with complex clinical and logistical hurdles, this set of preclinical results strongly supports allogeneic CAR-T," said Dr.
Mark Frattini, Senior Vice President and Head of Clinical Sciences at Cellectis.
Potential benefit of therapy in
AML.
UCART123
exhibits unprecedented selective cytotoxic activity in primary AML with minimal impact on normal cells, as reported in previous preclinical studies of CD123-targeted CARs Disadvantage
.

"References: 1.
https:// 2.
https://cellectis.
com/en/products/ucarts/3.
https:// 84.
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