BiCell Scientific is a front-runner in this life-changing medical breakthrough. It specializes in custom CAR T-cell development and validation through antibody manipulation, leveraging the power of CAR T-cells to accurately target tumor cells. BiCell develops precision antibodies with unparalleled binding specificity that deliver targeted assaults on tumor cell antigens like never before
“We’ve been making precision antibodies against single, small epitopes for years, and that gives us an edge in developing custom CAR T-cells that precisely bind with tumor cell antigens,” says John Hou, CEO.
At BiCell, engineering CAR T-cells involves a three-step process that begins with screening for a suitable antibody. The binding affinity is then adjusted depending on the therapeutic goal, and specific CAR T-cell therapies are created through affinity maturation and degeneration.
The next critical step involves manipulating the linker region in the ectodomain of the CAR fusion protein. A longer linker makes the antibody more flexible and encounters less spatial hindrance. In contrast, a shorter one does the opposite but makes the receptor more rigid, transducing the signal better to the intracellular domain. BiCell has mastered the balance between deciding the best course of action and effectively manipulating the linker sequence.
Two layers of manipulation are implemented in the intracellular domain–the final step of CAR T-cell engineering. The first layer enhances cell activity by focusing on the ITAM motifs, which act as a tyrosine receptor with critical sites that become phosphorylated upon receptor activation. These sites are then manipulated by mutating them to an attenuated form, creating two variations–one with heightened sensitivity (wildtype form) and the other with reduced sensitivity (attenuated form). This intracellular manipulation significantly impacts cytokine signaling, allowing the company to control T-cell activity.
The second layer of manipulation incorporates a suicidal gene switch or immortalization gene switch into CAR-T cells. Suicidal CAR-T cells expressing a concatenated Herpes simplex virus thymidine kinase SR39 protein, when bound with Ganciclovir, kill CAR-T cells. Immortalized CAR-T cells express a concatenated human telomerase reverse transcriptase (TERT) that immortalizes CAR-T cells.Success stories demonstrating BiCell’s unmatched expertise in antibody manipulation are numerous. In one instance, it was approached by a biotech company in California to customize CAR viruses for rodent models to track how efficiently CAR cells bind to tumor cells. To measure, the client planned to replace the standard green fluorescent protein (GFP) marker. BiCell developed a custom CAR virus, replacing GFP with a smaller, non-disruptive marker. This allowed the client to proceed with pre-clinical testing, confident in the CAR T-cells’ efficacy and clinical viability.
The antibody manufacturing and CAR T-cell development services are complemented by virus packaging and antibody humanization, which are critical for clients moving from pre-clinical to clinical stages. Depending on the project requirements, BiCell packages both retroviruses and lentiviruses and delivers CAR viruses in a ready-to-use, concentrated form, saving customers considerable time and resources. Antibody humanization involves modifying rodent antibodies and minimizing the risk of unforeseen immune responses, guaranteeing safe clinical trials for human applications.
Academic clients who constantly test theories and push the boundaries of innovation demand added flexibility. BiCell offers them the tools to ace their goals, including experimental features like adding GFP markers or suicidal proteins to CAR T-cells. This allows researchers to control T-cell activity and closely monitor the cells’ self-destruction at certain stages of pre-clinical tests and experiments.
We’ve been making precision antibodies against single, small epitopes for years, and that gives us an edge in developing custom CAR T-cells that precisely bind with tumor cell antigens
A commitment to instilling unparalleled precision and control in CAR T-cell therapy drives the company’s success. Whether working on high-affinity antibodies or fine-tuning linker regions, every project is handled with the same level of expertise and attention to detail. By combining precision antibody engineering with advanced CAR T-cell development, BiCell is laying the foundation of biomedical research.


