A New Attack on Blood Cancer

The scientists and startups hunting ROR1

1. Monoclonal antibody (mAb)

By 2015, ROR1 was known to be fairly specific to cancer cells. The Kipps Lab at UCSD designed a monoclonal antibody (mAb) called cirmtuzumab, which binds onto ROR1 and initiates a biologically-encoded cell-killing routine.

2. Chimeric antigen receptor T cells (CAR-T)

Along with cirmtuzumab, Oncternal is also developing an anti-ROR1 CAR-T.

CAR-T therapies are highly effective but challenging to manufacture [L&LS].

3. Bispecific T-cell engagers (BiTEs)

Many risks of CAR-T can be mitigated with bispecific T-cell engagers (BiTEs).

This BiTE binds to ROR1 on cancer cells and CD3 on immune cells. [Fig 1A, Qi et al. 2018]

4. Antibody-drug conjugate (ADC)

In addition to the UCSD mAb; the CAR-Ts from Oncternal and Fred Hutch; and the BiTEs from UCL and Scripps; NBE-Therapeutics is developing an antibody-drug conjugate (ADC) against cells with ROR1 on their surface.

Conclusion

Which of these four strategies — mAb, CAR-T, BiTE, or ADC — will be the most effective against cancer? While we’re still years from definitive data, my guess is that BiTEs like the one from the Rader Lab will yield the highest utility.

Blue: early-stage cancer. Red: late-stage cancer. Mice given placebo (left, vehicle) were terminally ill within a month, but mice given the Rader Lab BiTE (right, R11 x v9) were completely cured. [Figure 5A, Qi et al. 2018]

Principal at RA Capital, on the boards of 7 biotech companies. Founder/CEO of Nivien Therapeutics. Australian-American. 50 countries and counting.

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