Just trying to understand this.
Tumors with high Pre TIL count are more immunogenic tumors that ultimately are more susceptible to DCVax-L charged t-cells.
However, some/fewer tumors with very low (even zero in some cases?) Pre TIL count also respond to DCVax-L. While less immunogenic, DCVax-L appears to have charged the correct t-cells even though the low immunogenic (but aggressive) tumor did not have many mutant antigens.
Question: Why could DCVax-L do the latter but apparently the body's natural defenses never could raise an attack against the lower immunogenic tumors (less target antigens)?
Observation: DCVax-L dendritic cells are loaded with tumor lysate antigens that cannot suppress the DC during the pulsing process, whereas normal DCs naturally in the tumor would not have time to locate a fewer number of neoantgens before they were suppressed.
Therefore maybe this can be somewhat quantified?
In a new tumor, (many of which actually mutated over the course of many years before becoming detectable/aggressive), certain tumors that can become aggressive sooner with fewer mutations are more likely to escape the body's ability to detect them. Moreover, even when DCs do detect them, they are more likely to be suppressed by regulatory/suppressor cells as a function of:
1. time on location to detect (meaning the longer DCs must remain to find mutations, the more likely they will be suppressed)
2. number of suppressor cells already present
Thus, the reason DCVax-L can still affect these low immunogenic tumors in some cases might be that they are pulsed without any tumor microenvironment suppression while ex vivo, and even though the correct specific t-cells DCVax-L ultimately charges to seek and destroy have less to go on, they ultimately locate and attack the low immunogenic tumor. However, because there are less target antigens on each tumor cell, the tumors can more easily use checkpoint inhibitors to deal with a less overwhelming t-cell attack.
Therefore DCVax-L must utilize a way to block checkpoint molecules, particularly in less immunogenic tumors. Thus the need for adding CIs.
Again, I'm just trying to understand this.
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