Biotech Values

[swampboots]

"In cancer research, the total efficacy of combination therapy is less than the sum of the parts, not more."

IMHO: Because the forces acting on a mechanism may require combinations to allow any part to work, the forgoing statement should not be accepted as worthy of merit. This link I previously posted on the acknowledged value of combination therapy summed up in a recent article in Nature elaborates on the suspected value of a combination of therapies to activate a therapy which could not function without the necessary circumstances elicited by some other theraputic parts.


This just out from Nature:
https://www.nature.com/articles/nrc3153

But from the complex article notable the Neo-antigens mentioned ( in this conclusion part), and in my mind see it as a last stage tool in combination therapy, once the A team of best initiatives and strategies get selected along with the most powerful biomarkers (still awaiting better selection) vouching for each contributing novel agent's
order of effectiveness.:
"Future plans: combination therapy

It is obvious from both preclinical models and clinical trials that combinatorial approaches may be required for optimally effective and broadly applicable cancer immunotherapy. The scientific literature provides evidence for many potentially useful combinations, including: vaccines that allow for the improved priming of T cells and improved antigen presentation; methods that lead to enhanced T cell number and function, such as ACT; agonistic TNFR-targeted antibodies and cytokines; the suppression of inhibitory immune checkpoints using antibodies against CTLA4 and PD1; and lymphodepletion or other means of suppressing the inhibitory effects of regulatory T cells.

Recent work in cancer genomics has suggested another strategy for optimizing immunotherapy approaches. Sequencing the genomes of human breast and colon carcinomas showed that there were almost 100 missense mutations per tumour56. Analysis of these mutations using epitope-prediction algorithms suggested that a large fraction of these mutations might create neo-antigens with the potential to be recognized by the immune system57. Although these are largely random and vary from tumour to tumour, their presence suggests that agents that kill tumour cells without suppressing immune responses could be used to prime T cell responses, which could then be expanded and sustained by immune-checkpoint blockade58. Thus radiation, some chemotherapies, hormone ablation and therapies that target signalling pathways in tumour cells can be viewed as immunosupportive vaccines that would liberate multiple neo-antigens that, in combination with immune-checkpoint blockade, might result in a multipronged and effective immune attack.

Currently, we lack predictive diagnostic biomarkers to rationally choose combinations of immunotherapy for individual patients or cancer types. In addition, the timing or sequence of immunomodulatory interventions might be important because the kinetics of immune reactions have a crucial functional role. Therefore, preclinical data for promising combinations are necessary, with subsequent clinical trials, to evaluate the efficacy of novel combinations. Combination therapies are currently being tested in a few ongoing clinical trials including: ipilimumab plus radiation therapy in a randomized Phase III trial enrolling patients with metastatic prostate cancer (ClinicalTrials.gov identifier NCT00861614); ipilimumab plus leuprolide acetate hormonal therapy in a Phase IIa study in patients with localized prostate cancer (NCT01194271); ipilimumab plus androgen-deprivation therapy in a Phase II study in patients with metastatic prostate cancer (NCT01377389); and ipilimumab plus a PD1-targeted antibody in a trial in patients with metastatic melanoma (NCT01024231). An abstract that was presented at the 2011 American Society of Clinical Oncology (ASCO) annual meeting reported results from a Phase I trial of ipilimumab plus bevacizumab, an antibody that targets vascular endothelial growth factor A (VEGFA), in patients with melanoma; these preliminary data indicated that 14 out of 21 patients had partial responses and/or stable disease lasting >6 months59. There are also combination clinical trials with sipuleucel-T that are in the early stages of development and that are expected to begin patient accrual within the next year. The data from these trials are eagerly awaited and will help to guide the design of future combination studies."