Vor Biopharma and Janssen Collaborate on Novel Combination Therapy for Acute Myeloid Leukemia Using Engineered Stem Cells and Bispecific Antibodies

On July 8, 2021, Vor Biopharma Inc. announced a collaboration agreement with Janssen Biotech, a subsidiary of Johnson & Johnson. The collaboration will combine Vor’s proprietary engineered hematopoietic stem cell (eHSC) technology platform with Janssen’s investigational bispecific antibody therapy for acute myeloid leukemia (AML) to develop an innovative combination therapy for AML.

In cell therapy, Vor's eHSC platform features a novel mechanism of action and is frequently used in combination with other targeted oncology therapies. In some cases, the therapeutic target is expressed on the surface of both tumor cells and healthy cells. Consequently, while accurately binding to their intended target during their "tumor-eliminating" mission, these targeted therapies may also inadvertently damage healthy cells (on-target, off-tumor effect), resulting in treatment-related adverse events.

▲ Targeted cancer therapy may inadvertently damage healthy cells (Image source: Vor Bio official website)

On the eHSC platform, researchers utilize CRISPR/Cas9 gene-editing technology to engineer stem cells by knocking out the genes encoding the target protein. When these genetically engineered stem cells are infused back into the patient, they continuously generate new cells that no longer express the target protein of the targeted therapy. Consequently, the healthy cells are effectively outfitted with an “invisibility cloak,” sparing them from off-target drug toxicity. This enables the targeted therapy to operate without constraints, focusing exclusively on eradicating tumor cells.

▲Mechanism of Action of the eHSC Platform (Image source: Vor Bio official website)

Taking VOR33, an investigational therapy in Vor Bio’s development pipeline, as an example: in patients with acute myeloid leukemia (AML), tumor cells highly express the CD33 protein on their surface. Previous large-scale genomic studies have shown that many blood cells can remain healthy and viable without expressing CD33. Therefore, by knocking out the CD33 gene in hematopoietic stem cells ex vivo and reinfusing them into the patient to reduce the number of healthy cells expressing CD33, CD33-targeted therapies can achieve enhanced specificity while minimizing potential side effects.

Note: The original text has been abridged.

References:

[1] Vor Biopharma Announces Collaboration with Janssen to Develop Engineered Hematopoietic Stem Cell Transplants Combined With a Bi-Specific Antibody Therapy for Acute Myeloid Leukemia (AML). Retrieved July 8, 2021, from https://www.globenewswire.com/news-release/2021/07/08/2259858/0/en/Vor-Biopharma-Announces-Collaboration-with-Janssen-to-Develop-Engineered-Hematopoietic-Stem-Cell-Transplants-Combined-With-a-Bi-Specific-Antibody-Therapy-for-Acute-Myeloid-Leukemia.html

▽Follow 【WuXi AppTecDe】WeChat Official Account