Why Has Active Immunotherapy Not Worked in Lung Cancer?

Why Has Active Immunotherapy Not Worked in Lung Cancer?

A. Thomas; G. Giaccone  Ann Oncol. 2015;26(11):2213-2220.


Vaccines that rely on active specific stimulation of the host immune system have the potential to trigger durable antitumor responses with minimal toxicity. However, in nonsmall-cell lung cancer (NSCLC), several large phase III trials of vaccines reported within the last year have yielded disappointing results. Compared with placebo, belagenpumatucel-L (an allogenic tumor cell vaccine), tecemotide (a peptide vaccine targeting MUC-1) and melanoma-associated antigen-A3 (a protein-based vaccine) did not improve outcomes in NSCLC. The lack of clinically significant outcomes, despite their ability to prime and expand tumor antigen-specific T cells could at least partly be attributed to the inability of vaccine-induced T-cell responses to overcome the tumoral mechanisms of immune escape which limit the clonal expansion of T cells following vaccination. THE CANCER CELLS ARE SMART IMMUNOLOGICLALLY HERE ARE SOME WAYS THEY DEFEBD THEMSELVES AGAINST VACCINES AND REVVING UP THE IMMUNE SYSTEM A number of such mechanisms have been recognized including reduced antigen presentation ( THE CANCER ELLS MANAGE TO BLIND THEMSELVES TO THE VQCCINE AND NOT LET THIER ANTIGENS -FINGERPRINTS BE SEEN, antigenic loss, cytokines, THE BODIES OWN CHEMICALSA USED INSTEAD AGAINST THE VACCINE DELLS  immunosuppressive cells and immune checkpoints STRATEGIC POINTS IN THE CASCADE OF EVENTS IN THE IMMUNE SYSTEM THAT EVENTUALLY LEAD TO ATTACK AND DEATH. Strategies aimed at modulating the immune checkpoints have shown promise and are on the verge of revolutionizing the therapeutic landscape of metastatic NSCLC. Overcoming immune tolerance and improving the activation of antitumor T cells via combinatorial approaches may represent a new and more promising therapeutic application for active immunotherapies in NSCLC. WE ARE CLOSE TO OUTSMARTING THE CANCER CELLS- NOT THRE YET BUT IT IS JUST A MATTER OF TIME AS WE KNOW A MAJOR AREA TO FIGHT


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