Four Major Breakthroughs Made in Past 2018

Posted by beauty33 on September 22nd, 2019

1. APC Technology Helps with Large-Scale Expansion of CAR-T Cells

The modified T cells require extensive expansion before treatment, but this step is also time and cost consuming. In in vivo assays, assisted T cells with antigen presenting cells (APCs) can be expanded in large quantities in a short period of time, but in vitro, this process is not so easy.

In January of this year, Nature Biotechnology published a study from Harvard University’s Wyss Institute. Professor David J Mooney and his team developed a scaffold made of biomaterials that mimics the function of APC in vitro and makes T cell expansion more efficient. This scaffold is filled with interleukin 2 (IL-2) in a porous silicon rod-like material, which is a type of factor produced by APC that prolongs the life of T cells. There is a layer of lipid bilayer on the outside that mimics the cell membrane of APC. Later, they added a variety of antibodies that activate T cells.

These APC scaffolds are surprisingly efficient compared to conventional in vitro amplification techniques (Dynabeads), which can bring more benefits as soon as possible for patients if widely used in clinical practice.

2. An unexpected breakthrough: disruption of TET2 greatly enhances CAR-T effectiveness

In May of 2018, Nature’s previous study showed that researchers in a clinical trial of patients with CD19 chronic lymphocytic leukemia found that one patient did not appear obvious response until 2 months after receiving a second dose of T cells. The response was followed by complete remission, and the patient remained alive after the 5-year follow-up.

The researchers analyzed the T cells in this patient and found that 94% of the CAR-T cells in the patient were from the same ancestor. This surprising phenomenon results from the fact that during the genetical engineering with lentiviral transfection, the CAR sequencing was inadvertently inserted into an allele called TET2, causing dysfunction of the gene. However, the TET2 disorder makes the CAR-T cells in the renamed patients more proliferative, more resistant to cancer, and longer live.

Although this is the result of a single case, it is expected to be replicated in other clinical trials.

3. Stronger CAR-T: Scientists develop CAR-T cells carrying PD-1 antibodies

The study, published in the Nature, comes from the Memorial Sloan Kettering Cancer Center in the United States, where researchers succeeded in enabling 2nd generation CAR-T cells to secrete PD-1 antibody single-chain variable region fragments (scFv) while improving the anti-cancer activity of T cells in the tumor environment. The anti-tumor treatment effect is even better than the effect of CAR-T combined with PD-1 antibody. In the second phase, these scFvs are secreted near the tumor and do not enter the blood circulation, which makes the anti-tumor activity of CAR-T higher and longer, while ensuring lower side effects.

Researchers are currently designing clinical trials, hoping that this custom-made car-t cell can be applied to patients in the future.

4. Besides T cells, NK cells can also fight cancer

Researchers at the Dana-Farber Cancer Institute at Harvard Medical School screened a monoclonal antibody called 7C6 that allows NK cells to recognize and kill cancer cells.

MICA and MICB proteins can be expressed on tumors and serve as a signal to the immune system. But tumors usually cover themselves by shed these proteins, preventing specialized natural killer NK cell recognition and destruction.

This method effectively locks MICA and MICB to tumors, enabling NK cells to discover that they are eliminated. The antibody exhibits preclinical efficacy in a variety of tumor mouse models, including melanoma. In addition, this NK cell-mediated tumor lysis also reduced lung cancer metastasis.

About Creative Biolabs

As a global company, Creative Biolabs has more than 200 talented and well-trained scientists located in different continents working closely with partners from the entire world to develop and produce medicines of tomorrow. Specifically, the established leading experts in TCR and CAR T&NK cell immune therapy development offer the one-stop custom services that cover the entire new drug development pipeline, and an exclusive line of ready-to-use TCR and CAR T&NK cell construction products, such as virus packaging, purification, expansion and titer determination kits. Furthermore, a unique unparalleled CAR construction and production platform has been built up for all four CAR generations.