New "kid" on the therapy block

[ThreeWs]

No direct experience with ADCT-402 but never short on being curious and sharing uncredentialed opinion. For those who have not previously heard of ADCT-402 it is a monoclonal antibody (mAb) that targets CD19, a cell surface protein feature that is expressed on B-CLL cells in sufficient quantity to make it a desirable target. This is a similar approach that is used by mAbs that target CD20 such as Rituxan or Obinutuzumab with a twist in that a cytotoxin (SG3199), acting as the CLL cell assassin, is attached biochemically to the CD19 seeking part of ADCT-402 . Having SG3199 as a feature of the drug bypasses the need for the patient’s immune response to do the cell killing as done with our more familiar CD20 mAbs that trigger the death of CLL cells by Complement-Dependent Cytotoxicity (CDCC), Antibody-Dependent Cytotoxicity (ADCC) or Direct Cell death mechanisms.

None of our CD20 mAbs are particularly effective as mono therapies likely due to the cancer’s influence in remodeling the microenvironments in which the cancer cells live. The hope is that ADCT-402 can use the potency of the cytotoxin SG3199 to overcome the CLL Bear’s resistance mechanisms thus making it a more effective mono therapy.

We are seeing a sort of competition race between CD targeted therapies developed as mAbs vs CARs (Chimeric Antigen Receptor targeting agents). CARs or CAR-T therapies have been employed targeting CD19 and using “trained” T-cells as enhanced natural cell-assassins whereas mAbs have traditionally been targeting CD20 in CLL and activating immune responses that are already a part of the patient immunity.

Another example of mAb vs CAR competition is with these technologies being developed to target ROR1, a nearly idiopathic or unique protein marker on B cancer cells. mAbs are cheaper to develop and make than CARs but will they be better? Stay tuned.

WWW

[Justasheet1]

Thanks Wayne. Sounds interesting indeed.

Jeff

[PlanetaryKim]

Thanks very much for this information and explanation, Wayne. It sounds very promising, and I now understand some of these concepts better as a result of your explanation. Competition always good for producing the best, most effective result.

kim

[DMary]

Thank you! That's a great explanation of these complex drugs in development. I'm in a trial and was placed on the "mab" only arm. While I'm responding well there is no expectation that the response will be complete or being very long lasting. This info was helpful.

[Cllcanada Top Poster CURE Hero]

The great hope for this monoclonal is in Richter's patients who fail RCHOP and PD-1 inhibitors... and have no other options. It has a 60% response in R/R diffuse large B cell lymphoma with about a 40% complete response rate...

onclive.com/conference-cove...

This uses a PBD dimer that cross links DNA and is highly cytotoxic

adctherapeutics.com/downloa...

adcreview.com/adc-universit...

~chris

[SouthFloridaLady]

You should consider joining “CLL Support Group” on Facebook.