DC-based vaccines Flashcards
How are DC-based cellular vaccines prepared?
It starts with leukapheresis, where you isolate leukocytes from the blood of the patient. You then take the monocytes or CD34+ precursors, culture them in vitro with growth factors, which will turn them into immature DCs. These immature DCs will be loaded with tumor specific antigens which will mature them. These will then be readministered into the patient.
What is the effect of DC-based cellular vaccines?
When administered the antigen loaded DCs will migrate to the lymph nodes where they will activate the CD8+ T-cells and give a robust cytotoxic T-cell response that will destroy the tumor cells.
What is Sipuleucel-T?
is a DC-based therapy that has been approved for prostate cancer. They use GM-CSF as growth factor and prostaticacid phosphatase as antigen. This therapy increases the survival benefit for patients (not really significant, only 4.5 months).
The side effects are not severe.
What can adjuvants in DC-based immunotherapy do?
Adjuvants for DC-based immunotherapy could increase the affect onset, strength and duration, the affect immune phenotype. It can compensate poor immune responsiveness and revers immune tolerance to tumor antigens. It can reduce the tumor antigen dose required, and facilitate enhanced vaccine antigen stability. It could also broaden the immune responses to the tumor antigen and enhance cross-presentation. Adjuvants that are commonly used are GM-CSF, TNF, PgE2 and TLR-L.
What is the optimal DC phenotype for cancer immunotherapy?
You want a high expression of CCR7, this will allow the DCs to migrate to the lymph node and instruct the T-cells. Also a high expression of CD80/CD86 for proper activation of the naïve T-cells. A high IL-12/IL-27 expression is also wanted for instructing Th1 cells and CTL cells.
You don’t want them to induce Th2 cells because they useless in cancer therapy.
What is an alternative for DC immunotherapy in allergy?
An alternative can be in vivo therapy with liposomes with antigens, adjuvants and targeting molecules bound. These don’t have to be liposomes, there are many other options. It is much more cost efficiently for patients with allergies and autoimmunity.
