Advances in the treatment of late stage melanoma
Cite this as: BMJ 2013;346:f1265
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The article on advances in the treatment of late stage melanoma (1) described in detail the use of biologic agents.
However, no mention was made of current research against this disease using therapeutic vaccines. One such trial is currently being conducted in the UK. A plasmid DNA that encodes a human antibody molecule is injected into the patient. The molecule has been engineered to express a melanoma antigen called Tyrosinase-Related Protein 2 (TRP 2)and has two helper T cell epitopes attached to it. The antibody is then taken up by dendritic cells resulting in the recruitment of T killer cells and hence a direct immune response against melanoma cells expressing the TRP2 antigen.
In December 2012 the company involved in the trial of this therapeutic vaccine gave an update (2). It was part 1 of a Phase 1/2 clinical trial in patients with stage iii/iv malignant melanoma. Although a very small study (total of 13 patients) there were some encouraging results: one patient with multiple tumour lesions had a differential response to treatment including partial or complete regression of all lung metastases; two patients who had had all of their tumours removed prior to the trial were still disease-free more than a year after first dosing.
Biologic agents generally work by blocking unwanted activity whether it is by inhibiting auto-immunity in diseases such as Ankylosing Spondylitis, or by stopping cell division in cancerous lesions.
A therapeutic vaccine, however, works by stimulating the immune system into targetting cancerous cells and actually destroying them.
An analogy could be made with bacteriostatic and bacteriocidal antibiotics. Crudely speaking, in treating cancer, biologic agents are like the former and therapeutic vaccines equivalent to the latter.
Probably the greatest difficulty in treating cancer is getting the immune system to respond. I am sure that targetting the immune system is the way forward in cancer research, and that biologic agents will play a very important role in future cancer treatment, but I believe that therapeutic vaccines will have an even greater impact.
1 BMJ 2013;346:f1265
Competing interests: I am a shareholder in Scancell Holdings
MOD, Frampton Mansell Gloucestershire
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i have enjoyed this piece not because i am in any position to refute or authenticate what it seeks to sell (an idea) but because as a surgeon constantly working within body depths and recesses, and constantly re-sculpting gross anatomy to redeem errant conditions inflicted by a morbid anatomy (be these neoplastic or non-neoplastic), i am increasingly beginning to see how re-sculpting at the molecular level may prove the ultimate and more durable strategy to cancer control.
The science understandably is still imperfect but its seed is virile and only needs fertile minds to grow it.
Human biology must be the ultimate teacher in these areas; revealing to us the constant tendency of a body to harm itself through the activities of a few but threateningly placed mischievous signalling agents hijacking regulatory pathways and pushing the entire being down a steep slope into expiry.
To be able to understudy the body's own means of keeping these molecular mischief makers in check, locate the strategic game-changing triggers and harness them onto the winning side of a beleagured physiology is the ultimate means in my view of how we can work with the body to protect the body.
it boils down to expanding nature to keep nature's frontiers intact.
As i read about cytokine modulators and monoclonal antibodies being deployed into these frontiers, seeking to beat intracellular 'anti-molecularists' at their own game, i can only feel upbeat that a fighting phalanx complementary to the surgeon's knife, and with a more logical battle-winning tactic is on the horizon.
what is left is a more operational knowledge of these molecular pathways, greater familiarity with how to construct to be able to distinguish 'friend from foe' and so deliver a coup fatal only to the right spot.
By its logical conclusion ( whenever that finally comes), molecular manipulation will spell the eventual death of surgeons like us who still believe in weilding little else but a knife in a battle better won within the cells than anywhere else.
That said, i will still be slow in applying these biological agents to my patients knowing the art is still rather messy
full of hopes that future generations of similar patients will have a neater and more biased therapeutic regime in their armouries.
It is an inescapable fact, that to end it all well and profitably in the world of cancers, we need the continuing attention of basic science to all of the choreographies daily playing out within our cells; all of the cybernetics, the cross- molecular talks, straight or riddles
Competing interests: None declared
justin fadipe centre, mero heights. commonwealth of dominca
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