"Spot type" red blood cells treat a variety of cancers. Preclinical data reveals its characteristics. Yi Mai Meng broke the news

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Click on the picture and sign up now July 19, 2021 / Yi Mai Ke News eMedClub News/---Clinical-stage red blood cell therapy company Rubius Therapeutics (NASDAQ stock Code: RUBY), recently announced the publication of preclinical data of its leading clinical oncology project RTX-240 in the peer-reviewed journal Cancer Immunology, Immunotherapy, entitled "Anti-tumor efects of RTX-240: an engineered red blood cell" expressing 4‑1BB ligand and interleukin‑15”
.

Positive data confirms the potential of this therapy in the field of tumor treatment and supports clinical transformation
.

RTX-240 is a "off-the-shelf", allogeneic, engineered co-expressing 4-1BBL and IL-15TP red blood cell therapy; designed to stimulate 4-1BB and IL-15 pathways to activate and amplify T Adaptive and innate immunity of cells and NK cells to produce a powerful anti-tumor immune response
.

RTX-240 is currently undergoing a Phase 1/2 study as a single agent and combination therapy for patients with relapsed/refractory acute myeloid leukemia and solid tumors
.

▲ The structure of RTX-240 (picture source: rubiustx) The development of RTX-240 is based on Rubius' RED PLATFORM® platform
.

The preparation process of "spot type" red blood cell therapy includes: collecting CD34+ hematopoietic stem cells from a single healthy volunteer with type O blood, genetically modifying the cells through viral vector transfection technology, and then expanding and directional differentiation of the cells to make It differentiates into mature non-nucleated red blood cells, which are finally made into cell therapy products
.

Because there is no cell nucleus, therapeutic red blood cells do not have allogeneic rejection, which has a wider applicability to patients, and there is no need to worry about the impact of edited genes on the human body
.

▲ RED PLATFORM platform (picture source: rubiustx) For more details, scan the QR code for a complete read.
The preclinical studies announced this time mainly verify the following features of RTX-240: ➤ Amplification and activation of immune cells: in vitro study It shows that RTX-240 exerts a synergistic effect through the 4-1BB and IL-5 pathways, causing the activation and expansion of NK and T cells
.

In mouse melanoma and colon cancer models, based on the "mouse version" mRBC-240 of RTX-240, activated T cells and NK cells significantly inhibit the growth of tumors in the body; ➤ Improved safety features: engineering Red blood cells follow the same distribution and elimination pattern in the body as endogenous red blood cells, and the organs have small accumulations
.

The biodistribution results show that mRBC-240 is mainly limited to the circulatory system and spleen of mice, so the toxicity is small; ➤ Better tolerance: Some 4-1BB agonistic antibodies have strong anti-tumor effects, but are also dose-dependent Liver toxicity limits the clinical development of these therapies
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Compared with the 4-1BB agonistic antibody, mRBC-240 is still well tolerated at the highest dose, and there is no basis for liver damage, which also means that RTX-240 shows a wider therapeutic window
.

▲ RTX-240 directly activates CD8+ T cells and NK cells in vitro (picture source: springer) Laurence Turka, Chief Scientific Officer of Rubius, said: “These preclinical data prove the mechanism of action of RTX-240.
So far we have also seen To transform it into clinical
.

"Rubius will also recruit more patients in the ongoing phase 1/2 clinical trials of RTX-240
.

Rubius Therapeutics was established in 2013 by the top medical VC Flagship Pioneering in the United States, and listed on the Nasdaq in 2018
.

Rubius is currently focusing on the field of cancer and autoimmune diseases
.

In addition to RTX-240, there are three other red blood cell candidate products in its R&D pipeline, namely RTX-321 (RTX-aAPC) for HPV 16-positive tumors, for use in entities RTX-224 for tumors and RTX-T1D for type 1 diabetes
.

▲ Rubius' pipeline (picture source: rubiustx) Red blood cells have been used as carriers to deliver drugs for nearly half a century.
Red blood cell-based drug delivery systems have Its excellent biocompatibility, circulatory half-life, safety and many other advantages have received extensive attention in clinical transformation
.

Red blood cell-based drug delivery systems have also developed from traditional methods such as encapsulation and surface adsorption to the use of enzyme engineering covalent modification, A whole new generation of technologies such as genetic engineering
.

Recently (July 15), West Lake Biomedical Technology (Hangzhou) Co.
, Ltd.
, the first domestic company focusing on red blood cell therapy, received a financing of 100 million yuan
.

West Lake Biotech established a red blood cell engineering transformation platform , Through the targeted transformation of red blood cells to carry drugs for the treatment of various major diseases, and successively developed a variety of innovative treatment products for major diseases such as cancer, infectious diseases, gout, rare diseases, autoimmunity and metabolism
.

It is aimed at cancer Clinical research projects initiated by multiple investigators have been reviewed and approved by the ethics committee
.

Recommended reading: Medicine FinancingWest Lake Biopharmaceuticals has received another 100 million yuan in financing, and additional investment by old shareholders such as Sequoia China, Sidao Capital, Chende Capital, etc.
Reference materials: 1.
https://link.
springer.
com/content/pdf /10.
1007/s00262-021-03001-7.
pdf2.
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