Great discussion regarding some of the potential side effects of a combined treatment with CAR T cells.
I think it is important to keep in mind that Prof Yuman Fong designed CF33 to be an effect cancer cell killer in its own right and that the combination therapy with CD19 CAR T is meant to be a secondary "value added" mopping up and killing activity for any remaining cancer cells.
I have selected and displayed below a few slide from Yuman's presentation and slides from July 2019:when Imugene acquired CF33.
Please take a few minutes to review each of these slide. Read and think about the information. CF33 shows outstanding potential from the many mice trials.
Some key points from his presentation to think about:
- Preclinical data hasdemonstrated that CF33 ismore efficacious than allparental viruses and someviruses in clinical trials.
- Especially impressing is thatCF33 can shrink multipletypes of cancer at anextremely low dose (1000PFU).<< During his talk he mentioned that other drugs often require does many times higher (millions PFU) than CF33. You can give a patient multiple doses unlike other drugs.
- Importantly, CF33 shrinksnot only injected tumors,but alsonon-injected distanttumors (abscopal effect). << Once it enters the persons body, it will seek out and infect cancer cells elsewhere in the body.
- << Yuman also mentioned it is a unique virus never before been seen on earth - they designed and created it as a cancer cell killer. Listen to his Youtube presentation.
- DNA virus - Much easier to manipulateand vectorize to carry foreign gene astherapeutic payloads. << Yuman said we need to think of CF33 as a platform and not just a signal use cancer drug.
- CF33 - more potent in terms of;a) Range of cancer cell typesinfectible; b) Low doses necessary for cancerkilling in vitro and invivo; andc) Therapeutic window (dose fortoxicity minus dose for efficacy).
- CF33 can be used in multiple doseswithout complete neutralization byhost immune system. << Flexibility in the way CF33 can enter a person's body for treatment. CF33 will find its way.
- In data published in Journal Translational Research, no viral sheddingin blood and urine was found. No signs of illness were found andanimals ate well and gained weight.
- In total, more than 500 mice have been treated with derivatives fromthis back bone. More than 50 mice have been treated with doses up to10E7 IV and IT without signs of toxicity. << During his presentation (Youtube) Yuman mentioned that they had gone further and tested 700 mice.
- CF33 SHRINKS TRIPLE-NEGATIVE BREAST CANCER. Mice treated with bothintratumoral virus and IV - The viral dose used was 2-5 orders of magnitude lower than doses used for oncolytic viruses under clinical testing. << Small does of CF33 are very effective and this should hopefully this means a reduction in the magnitude of any potential negative side effectives, if any do surface. Animal trials suggest safety.
- CF33 OUTPERFORMS AMGEN & GENELUX VIRUSES. << Sounds very promising.
- CF33 ABSCOPAL EFFECTS. The abscopal effect describes a situation whereby shrinkageof untreated or distant tumors occurs concurrently withshrinkage of tumors directly treated with the drug. << CF33 is a cancer cell seeking BEAST throughout a person's body !!!
- Tumors can be killed by as little as 10E3viruses (2-3 logs lower than any othervirus in human testing). << Impressive
- Virus was tested against T-vec (Amgenproduct) and GLONC-1 (Genelux), and ismany times more effective in infectingand killing cancer. << Outstanding / Mind blowing
- Spread of (CF33) virus to and killing non-injectedtumors& Regression of tumor that did not have viralspread.
ConclusionCF33 is a mighty fine cancer cell seeking, retardation & killing virus in its own right using low doses and multiple doses if needed
With flexibility in how it can be administered to a patient.
CF33 will seek out other cancer cells in the patients body via it abscopal effect capabilities.
CF33 is many times more effective than T-vec (Amgenproduct) and GLONC-1 (Genelux) in infectingand killing cancer.
>>> So any CF33 combination therapy with CD19 CAR T cells is an added bonus.I am really looking forward to the upcoming CF33 Phase I clinical trials and its results.
The slides discussed above:
(20min delay)