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h R 1 In the short communication “Endogenous retroviruses expressed in uman tumours cannot be used as targets for anti-tumour vaccines ” 1] Joachim Denner argues that the idea we recently proposed [2] lacks cientific basis and may be harmful. We do not agree with these stateents. In the short communication, it is argued that animal studies have not een able to demonstrate sufficient effectiveness of endogenous retroirus (ERV) immunotherapy against murine cancers. While passive huoral and cellular immunity against murine ERVs, as Dr. Denner notes, s capable of slowing or controlling cancer growth, vaccination has also roven efficacious in a study omitted in the short communication: We ave previously shown that adenoviral vectors, known to be more poent than DNA vaccination, serve as a viable vaccination strategy against urine ERV expressing cancers [3] . Still, advancing from murine to huan ERVs (HERVs) in mouse models is not necessarily straightforward. ccordingly, Dr. Denner progresses to an acknowledgement of the efectiveness of passive immunotherapy in models of human cancer in mmunocompromised mice – models where for obvious reasons vacciation cannot be tested. As covered in our review, vaccination strategies ave however proven effective against murine tumor cell lines genetially modified to express HERV-K. Thus, we argue that data from mouse odels, including that presented by Dr. Denner, supports targeting ERVs s a viable approach for mobilizing the immune system to kill cancer ells. The next concern presented is the safety aspect of vaccinating against n antigen that is expressed in placenta and embryonic stem cells (ESC). hile the expression of HERV-K in the human placenta clearly warants caution when considering HERV-K directed immunotherapies for omen of childbearing potential, we must argue that a potential imune reaction against the placenta cannot be a sufficient argument o withhold cancer treatment for those accepting not to have further hildren. Patient education and oncofertility counselling are key factors ere. Likewise, the expression of HERV-K in embryonic and pluripotent tem cells is not a relevant concern at a level to preclude development f new cancer therapies. Indeed, active cancer immunotherapies delibrately targeting fetal antigens have been studied for more than a cenury, and several of the most intensively studied cancer antigens such s MAGE-A3 and NY-ESO-1 show prominent embryonic [4] and mesnchymal [5] stem cell expression, respectively. For such antigens there ave been clinical vaccine trials in phase 3 for MAGE-A3 [6] and a spe-