IF he bothered to READ the A-7 publications from the phase 2, he would see clear evidence of SYSTEMIC response.
One of the strongest IMMUNE responses is from a tissue MISMATCH caused by the great diversity in the Major Histocompatibility Complex (MHC), known as the Human Leukocyte Antigen (HLA) in humans
HLA B7 is the gene in A-7, and where the # 7 comes from.
The human leukocyte antigen (HLA) system is the name of the major histocompatibility complex (MHC) in humans. The super locus contains a large number of genes related to immune system function in humans. This group of genes resides on chromosome 6, and encodes cell-surface antigen-presenting proteins and has many other functions. The HLA genes are the human versions of the MHC genes that are found in most vertebrates (and thus are the most studied of the MHC genes). The proteins encoded by certain genes are also known as antigens, as a result of their historic discovery as factors in organ transplants. The major HLA antigens are essential elements for immune function. Different classes have different functions:
HLAs corresponding to MHC class I (A, B, and C) present peptides from inside the cell (including viral peptides if present). These peptides are produced from digested proteins that are broken down in the proteasomes. In general, these particular peptides are small polymers, about 9 amino acids in length. Foreign antigens attract killer T-cells (also called CD8 positive- or cytotoxic T-cells) that destroy cells.
HLAs corresponding to MHC class II (DP, DM, DOA, DOB, DQ, and DR) present antigens from outside of the cell to T-lymphocytes. These particular antigens stimulate the multiplication of T-helper cells, which in turn stimulate antibody-producing B-cells to produce antibodies to that specific antigen. Self-antigens are suppressed by suppressor T-cells.
HLAs corresponding to MHC class III encode components of the complement system.
HLAs have other roles. They are important in disease defense. They are the major cause of organ transplant rejections. They may protect against or fail to protect (if down regulated by an infection) against cancers. Mutations in HLA may be linked to autoimmune disease (examples: type I diabetes, coeliac disease). HLA may also be related to people's perception of the odor of other people, and may be involved in mate selection, as at least one study found a lower than expected rate of HLA similarity between spouses in an isolated community.
Aside from the genes encoding the 6 major antigen-presenting proteins, there are a large number of other genes, many involved in immune function, located on the HLA complex. Diversity of HLAs in the human population is one aspect of disease defense, and, as a result, the chance of two unrelated individuals with identical HLA molecules on all loci is very low. HLA genes have historically been identified as a result of the ability to successfully transplant organs between HLA-similar individuals.
Appreciate the sentiment. I have a lot to learn for working in this field for 45 years. Anyway, the trial design is powered to detect 80% survival advantage (11 to 18 months). Assuming the trial reaches target events the coming June (average 4+ years for all patients), the median would be somewhere between 20 to 24 months (standard design of 75% patients die, roughly equivalent to all stage IV patients with normal LDH from diagnosis, Balch et al., 2009) for the whole patient population. The million dollar question would be: does the trial design be able to detect, say, 16 and 24 months difference? Most likely not. By the way, I do believe A7 has some effect, just not enough for approval unless combined with Yervoy or anti-PD1 (most likely anti-PD-L1).