Honestly, I think this part is incorrect, and filled with suggestions from articles by competitors. The reference to 3-5 months, I don’t think that makes sense. And it would suggest that faster manufacturing would likely makes a huge difference but I honestly don’t think that is what happened in the Phase III trial. And they try to undercut the very data they provide… how could the results be as they are and yet the DC’s are not efficient in phagocytosis… they are looking to someone else’s research to say these things, which I do not think is truly about DCVax. These are generalizations from competitors. And the mRNA hypothesis is presented as fact, when it is not proven in reality.
It also undercuts what Dr. Liau said, that Glioblastoma is not standardized but very specifically different in each person with different antigens. They are saying you basically just need an mRNA vaccine that goes after cytomegalovirus and a few antigens, it’s cheaper, standardized and more practical. But that is not what other trials suggest. Yes, cytomegalovirus is even an antigens for DCVax, but we know the tumors evolve away with the approach they suggest.
Language right after the DCVax results they suggest:
Quote:
“Nevertheless, developing vaccines for individual neoantigens of patients is expensive and time-consuming because preparation of vaccines from the tumor samples take between 3–5 months (Peng et al., 2019). An additional limitation is the generation of sufficient DCs, as DCs comprise only < 1% of peripheral blood mononuclear cells. To overcome this obstacle, DCs were generated from monocytes ex vivo. However, it is questionable whether these monocyte-derived DCs compared to primary DCs from peripheral blood are efficient in an anti-tumor immune response (Huber et al., 2018). Furthermore, phagocytosis of tumor cells by APCs was enhanced by blocking the anti-phagocytosis molecule CD47 in combination with TMZ, inducing an effective anti-tumor immune response (von Roemeling et al., 2020). However, the use of whole tumor lysate to pulse DCs could cause autoimmune encephalitis since tumor lysate contains healthy brain tissue and induces an immune response toward the normal brain (Polyzoidis and Ashkan, 2014).
Moreover, a highly promising approach for cancer immunotherapy, denotes mRNA vaccine, which express tumor-specific antigens or TAA in APCs, has become into focus to treat glioblastoma. mRNA does not pose the risk of an infectious or an integrating agent, the potential of mRNA vaccines is the effectiveness, safety in administration, and low cost of manufacturing (Pardi et al., 2018; Weng et al., 2020). A phase I study utilizing DCs, loaded with TAA mRNA targeting cytomegalovirus pp65 protein that is expressed in > 90% of glioblastoma cases, demonstrated an OS of 35 months. As a consequence, co-delivery of mRNA vaccines together with immunotherapeutics can increase the host anti-tumor immune response (Batich et al., 2020; Miao et al., 2021). Notwithstanding the expected advantages, several factors limit the use of mRNA in therapy, including immunosuppressive effects of the tumor, half-life period of mRNA, and delivery complications in vivo (Vik-Mo et al., 2013; Weng et al., 2020). To overcome such issues, the chemical nucleotide modifications, capping analogs, and alternative delivery are currently being investigated and hold a great promise with current successful use of lipid nanoparticles to deliver mRNA vaccines (Weng et al., 2020; Rui and Green, 2021) or the use of viral vectors (Weng et al., 2020) and is therefore anticipated to increase the attention in glioblastoma immunotherapy.”
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