Dr. Weeks Comment: For the past decade, I have advocated that patients only accept cancer treatments which target the lethal cancer STEM cell. If you don’t know what the cancer STEM cell is, take time to listen to a lectures I have given HERE. And if you want to read some peer reviewed scientific literature, I invite you to study HERE, HERE and HERE.
Tragically, oncologists are not keeping up with the literature featuring safe and effective treatments for cancer STEM cells. Instead they are still targeting the relatively harmless cancer TUMOR cells and that is a disservice.
I have repeated for the past decade that the future of cancer treatment is 1) anti-inflammation and 2) immune enhancement because only the body heals itself and our task in healing is to support the body doing what it is able and willing to do: survive and thrive.
Now, we have a new promising immune therapy which unleashes the power of the body to recognize and kill cancer.
But don’t forget to target the cancer STEM cells. And these anti-inflammatory and nutrients dense seed drinks are the best I have found to get healthy.
NEW T CELL THERAPY
https://www.zerohedge.com/health/scientists-britain-may-have-just-accidentally-found-cure-cancer
RELATED RESEARCH
1.
Nat Immunol.2020 Jan 20. doi: 10.1038/s41590-019-0578-8. [Epub ahead of print]
Crowther MD1, Dolton G1, Legut M1, Caillaud ME1, Lloyd A1, Attaf M1, Galloway SAE1, Rius C1, Farrell CP2, Szomolay B1,3, Ager A1,3, Parker AL4, Fuller A1, Donia M5, McCluskey J6, Rossjohn J1,3,7,8, Svane IM5, Phillips JD2, Sewell AK9,10.
Abstract
Human leukocyte antigen (HLA)-independent, T cell-mediated targeting of cancer cells would allow immune destruction of malignancies in all individuals. Here, we use genome-wide CRISPR-Cas9 screening to establish that a T cell receptor (TCR) recognized and killed most human cancer types via the monomorphic MHC class I-related protein, MR1, while remaining inert to noncancerous cells. Unlike mucosal-associated invariant T cells, recognition of target cells by the TCR was independent of bacterial loading. Furthermore, concentration-dependent addition of vitamin B-related metabolite ligands of MR1 reduced TCR recognition of cancer cells, suggesting that recognition occurred via sensing of the cancer metabolome. An MR1-restricted T cell clone mediated in vivo regression of leukemia and conferred enhanced survival of NSG mice. TCR transfer to T cells of patients enabled killing of autologous and nonautologous melanoma. These findings offer opportunities for HLA-independent, pan-cancer, pan-population immunotherapies.
2.
J Biol Chem.2019 Dec 27;294(52):20246-20258. doi: 10.1074/jbc.RA119.009437. Epub 2019 Oct 16.
MacLachlan BJ1, Dolton G1, Papakyriakou A2, Greenshields-Watson A1, Mason GH1, Schauenburg A1, Besneux M1, Szomolay B1, Elliott T3,4, Sewell AK1, Gallimore A1, Rizkallah P1, Cole DK1, Godkin A5,6.
Abstract
CD4+T-cells recognize peptide antigens, in the context of human leukocyte antigen (HLA) class II molecules (HLA-II), which through peptide-flanking residues (PFRs) can extend beyond the limits of the HLA binding. The role of the PFRs during antigen recognition is not fully understood; however, recent studies have indicated that these regions can influence T-cell receptor (TCR) affinity and pHLA-II stability. Here, using various biochemical approaches including peptide sensitivity ELISA and ELISpot assays, peptide-binding assays and HLA-II tetramer staining, we focused on CD4+T-cell responses against a tumor antigen, 5T4 oncofetal trophoblast glycoprotein (5T4), which have been associated with improved control of colorectal cancer. Despite their weak TCR-binding affinity, we found that anti-5T4 CD4+T-cells are polyfunctional and that their PFRs are essential for TCR recognition of the core bound nonamer. The high-resolution (1.95 Å) crystal structure of HLA-DR1 presenting the immunodominant 20-mer peptide 5T4111-130, combined with molecular dynamic simulations, revealed how PFRs explore the HLA-proximal space to contribute to antigen reactivity. These findings advance our understanding of what constitutes an HLA-II epitope and indicate that PFRs can tune weak affinity TCR-pHLA-II interactions.
3.
J Immunol.2019 Oct 1;203(7):2023-2024. doi: 10.4049/jimmunol.1900968. Epub 2019 Aug 30.
Kim A, Han CJ, Driver I, Olow A, Sewell AK, Zhang Z, Ouyang W, Egen JG, Yu X.
4.
J Immunol.2019 Aug 15;203(4):1076-1087. doi: 10.4049/jimmunol.1801472. Epub 2019 Jun 28.
Kim A1, Han CJ1, Driver I2, Olow A3, Sewell AK4, Zhang Z5,6, Ouyang W1, Egen JG1, Yu X7.
Abstract
Elicitation of tumor cell killing by CD8+T cells is an effective therapeutic approach for cancer. In addition to using immune checkpoint blockade to reinvigorate existing but unresponsive tumor-specific T cells, alternative therapeutic approaches have been developed, including stimulation of polyclonal T cell cytolytic activity against tumors using bispecific T cell engager (BiTE) molecules that simultaneously engage the TCR complex and a tumor-associated Ag. BiTE molecules are efficacious against hematologic tumors and are currently being explored as an immunotherapy for solid tumors. To understand mechanisms regulating BiTE molecule–mediated CD8+T cell activity against solid tumors, we sought to define human CD8+T cell populations that efficiently respond to BiTE molecule stimulation and identify factors regulating their cytolytic activity. We find that human CD45RA+CCR7-CD8+T cells are highly responsive to BiTE molecule stimulation, are enriched in genes associated with cytolytic effector function, and express multiple unique inhibitory receptors, including leukocyte Ig-like receptor B1 (LILRB1). LILRB1 and programmed cell death protein 1 (PD1) were found to be expressed by distinct CD8+T cell populations, suggesting different roles in regulating the antitumor response. Engaging LILRB1 with its ligand HLA-G on tumor cells significantly inhibited BiTE molecule-induced CD8+T cell activation. Blockades of LILRB1 and PD1 induced greater CD8+T cell activation than either treatment alone. Together, our data suggest that LILRB1 functions as a negative regulator of human CD8+effector T cells and that blocking LILRB1 represents a unique strategy to enhance BiTE molecule therapeutic activity against solid tumors.
Copyright © 2019 by The American Association of Immunologists, Inc.
PMID: 31253728 PMCID: PMC6680066DOI: 10.4049/jimmunol.1801472
5.
Front Immunol.2019 Mar 13;10:319. doi: 10.3389/fimmu.2019.00319. eCollection 2019.
Peptide Super-Agonist Enhances T-Cell Responses to Melanoma.
Galloway SAE1, Dolton G1, Attaf M1, Wall A1, Fuller A1, Rius C1, Bianchi V1, Theaker S1, Lloyd A1,2, Caillaud ME1, Svane IM3, Donia M3, Cole DK1,2, Szomolay B4, Rizkallah P1, Sewell AK1,4.
Abstract
Recent immunotherapeutic approaches using adoptive cell therapy, or checkpoint blockade, have demonstrated the powerful anti-cancer potential of CD8 cytotoxic T-lymphocytes (CTL). While these approaches have shown great promise, they are only effective in some patients with some cancers. The potential power, and relative ease, of therapeutic vaccination against tumour associated antigens (TAA) present in different cancers has been a long sought-after approach for harnessing the discriminating sensitivity of CTL to treat cancer and has seen recent renewed interest following cancer vaccination successes using unique tumour neoantigens. Unfortunately, results with TAA-targeted “universal” cancer vaccines (UCV) have been largely disappointing. Infectious disease models have demonstrated that T-cell clonotypes that recognise the same antigen should not be viewed as being equally effective. Extrapolation of this notion to UCV would suggest that the qualityof response in terms of the T-cell receptor (TCR) clonotypes induced might be more important than the quantityof the response. Unfortunately, there is little opportunity to assess the effectiveness of individual T-cell clonotypes in vivo. Here, we identified effective, persistent T-cell clonotypes in an HLA A2+patient following successful tumour infiltrating lymphocyte (TIL) therapy. One such T-cell clone was used to generate super-agonist altered peptide ligands (APLs). Further refinement produced an APL that was capable of inducing T-cells in greater magnitude, and with improved effectiveness, from the blood of all 14 healthy donors tested. Importantly, this APL also induced T-cells from melanoma patient blood that exhibited superior recognition of the patient’s own tumour compared to those induced by the natural antigen sequence. These results suggest that use of APL to skew the clonotypic qualityof T-cells induced by cancer vaccination could provide a promising avenue in the hunt for the UCV “magic bullet.”
6.
Nat Commun.2018 Jul 13;9(1):2716. doi: 10.1038/s41467-018-05288-0.
Zhao X1, Sankaran S1,2, Yap J1, Too CT1,2, Ho ZZ3, Dolton G4, Legut M4, Ren EC5, Sewell AK4,6, Bertoletti A3, MacAry PA1,2,7, Brzostek J8, Gascoigne NRJ9,10,11.
Author information
Abstract
Foreign antigens are presented by antigen-presenting cells in the presence of abundant endogenous peptides that are nonstimulatory to the T cell. In mouse T cells, endogenous, nonstimulatory peptides have been shown to enhance responses to specific peptide antigens, a phenomenon termed coagonism. However, whether coagonism also occurs in human T cells is unclear, and the molecular mechanism of coagonism is still under debate since CD4 and CD8 coagonism requires different interactions. Here we show that the nonstimulatory, HIV-derived peptide GAG enhances a specific human cytotoxic T lymphocyte response to HBV-derived epitopes presented by HLA-A*02:01. Coagonism in human T cells requires the CD8 coreceptor, but not T-cell receptor (TCR) binding to the nonstimulatory peptide-MHC. Coagonists enhance the phosphorylation and recruitment of several molecules involved in the TCR-proximal signaling pathway, suggesting that coagonists promote T-cell responses to antigenic pMHC by amplifying TCR-proximal signaling.