RE: Question for Burble sand others who understand the science16 Jun 2022 08:24
Hi Martin,
In response to your question standard of care for advanced melanoma was generally just a checkpoint PD-1 inhibitor such as Pembrolizumab (Keytruda) or Nivolumab (Opdivo). Hence the original design for the trial focussing on Keytruda.
It has been shown in the clinic that combining a PD-1 inhibitor with a CTLA-4 inhibitor such as
Ipilimumab (Yervoy) resulted in better outcomes for patients and so for many this doublet treatment is now considered a standard of care. As such Scancell won’t have approached BMS per se, they’re most likely just adapting the trial to what patients are getting as standard of care.
Briefly and in lay terms - CTLA-4 inhibitors such as ipilimumab (yervoy) block CTLA-4 which regulates the growth and activity of T cells, in doing so activating the patient’s immune system against melanoma by allowing T cells to multiply and increase the immune response.
PD-1 inhibitors such as pembrolizumab (Keytruda) and nivolumab (Opdivo) block a different checkpoint molecule called PD-1, which helps protect tumor cells from being attacked by the patient’s immune system. These PD-1 inhibitors removes the PD-1 "shield" to allow a patient’s immune system to find and attack melanoma cells.
So one essentially turns on the immune response, allowing T cells to begin the attack on melanoma. The other then removes the immune protection that cancer cells put up to defend themselves from attacks.
Add in SCIB1 - which effectively ‘trains’ the T cells on what to identify and target within the melanoma. Could lead to a very potent response being mounted against the patient’s cancer.
The immune system brakes are off (CTLA-4), the tumours shields are down (PD-1) and the immune system knows exactly who the enemy is that they need to kill (SCIB1).
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