Comment on: Endogenous retroviruses expressed in human tumours cannot be used as targets for anti-tumour vaccines

Abstract

h R 1 ( In my short communication “Endogenous retroviruses expressed in uman tumours cannot be used as targets for anti-tumour vaccines ” [1] , indicated possible risk factors when human endogenous retroviruses HERVs), which are highly expressed in some human tumours and in he placenta, will be used as targets for tumour vaccination and imunotherapy. The main risk factors are expression of HERVs on human mbryonic stem cells (ESC), and on immune and other cells. Expresion on human ESC is well-documented [2] , expression on immune and ther cells is documented at least after infections (for review see [3] ). nteraction of the vaccine or therapy with these normal cells may be armful. In the accompanying comment, Holst and co-workers deny these risk actors [4] , partially not recognising the virological background. For exmple, in one of their studies in a mouse model [5] , they immunised gainst the melanoma associated retrovirus (MelARV) using an adenviral vector and prevented colorectal tumor growth and progression in ice. However, MelARV is not an endogenous retrovirus, it is a recominant virus not present in the murine genome. It is also not surprising hat immunisation against proteins of HERV-K, artificially expressed on he surface of mouse tumour cells, successfully reduced tumour growth n the mouse [6] . The HERVproteins are not expressed on mouse ESC nd mouse immune cells. In the human system, the authors claim that “existing HERV-Kpecific T cell responses induced in human breast and ovarian cancers oints towards a favorable safety profile ” [4] . However, in these studies ytotoxic T cells killing HERV-K-expressing tumour cells were induced nly in vitro , but not in vivo , in the patient [7 , 8] . These HERV-K-specific ytotoxic cells did not kill normal cells, but there were no investigations hether human ESC were among these normal cells. Further, the authors compare HERV antigens with fetal antigens. hey argue, that clinical vaccine trials in phase 3 for the fetal ntigen melanoma-associated antigen A3 (MAGE-A3) and a specific AR(chimeric antigen receptor)-T cell therapy targeting the New York sophageal squamous cell cancer-1 (NY-ESO-1) were performed withut specific safety signals. The truth is, that the study using MAGE-A3 ad been stopped [9] . Whereas the cancer testis antigen MAGE-A3 is ndeed expressed on human ESCs [10] , I was unable to find such data or NY-ESO-1. The authors claim that I ignore the fact that immune responses gainst antigens expressed on dendritic cells are a natural part of tuor immune responses, but I don ́t do this and this has nothing to do