Yet another successful cancer vaccine trial
In a Nature Letters article published in July 2017, a group from the Dana-Farber Cancer Institute led by Catherine Wu reported an exciting proof-of-principle study showing that a personal neoantigen vaccine is safe, strongly immunogenic, and capable of inducing tumor-reactive T cells.
Ott et al. Nature Letters 2017 used whole-exome sequencing of DNA from matched tumor and normal cells to identify somatic mutations and used HLA binding prediction algorithms to create personalized HLA-binding peptide sequences. Corresponding peptides were synthesized and used as immunogens administered with poly-ICLC in patients with previously untreated high-risk melanoma in a phase I study.
In conjunction with flow cytometry, the authors used Mabtech IFN-γ ELISpot assays to show that personalized neoantigen vaccines generate polyfunctional CD4- as well as CD8-specific T cell responses that persisted over time. They also showed that subsequent checkpoint blockade therapy (anti-PD1 mAb pembrolizumab) broadens the repertoire of neoAg-spec T cells. This study demonstrates that neoantigen vaccines could address the heterogeneity of tumors and minimize escape, and further suggests that synergy may be achieved with checkpoint blockage and other immunotherapeutics.Tuesday, August 22, 2017
Great news for RNA-based cancer vaccines
Very nice data from Sahin et al (Nature, 2017), showing that neo-epitope vaccination works in human subjects with melanoma.
The authors sequenced RNA from tumor biopsies to identify mutations that could serve as HLA-binding neo-epitopes. The resulting RNA-based vaccines were subsequently injected into a lymph node of the patient, and the idea is that dendritic cells will engulf the vaccine, translate the RNA-encoded antigens and present them to T cells.
The immunogenicity of the mutations was analysed by IFN-γ ELISpot pre- as well as post-vaccination. The promising post-vaccination results suggest that these kinds of patient-tailored vaccines may prevent recurrent disease in high risk patients, especially in combination with check-point blockade.
A very interesting bonus-finding was that a single mutation may give rise to neo-epitopes presented on different HLA class I molecules to different CD8+ T cell clones.
To find other references for Mabtech’s human IFN-γ ELISpot kits, please visit our Citations Database.Friday, July 7, 2017
Allogeneic dendritic cells as off-the-shelf immune boosters
Sweden-based Laurell et al (2017) think outside the box when they utilize allogeneic instead of autologous dendritic cells (DC) to enhance anti-tumor responses. These activated DCs are not used for antigen-presentation, but when injected into the tumor site they start a local inflammation and secrete pro-inflammatory cytokines and chemokines that attract and activate bystander autologous DCs. The autologous DCs will in turn engulf tumor debris, migrate to the draining lymph node and present tumor antigens to T cells.
Thus, this strategy uses the patient’s own tumor as antigen source in situ (double italics on that one!), circumventing the ordeal with producing tumor-antigen presenting autologous DCs in vitro. In addition, since there’s no MHC-restriction to account for, the allogenic DCs can act as an off-the-shelf immunogenic adjuvant for anti-tumor responses. Very cool.
Oh yeah, and of course the authors used Mabtech’s IFN-gamma ELISpotPLUS kit to evaluate tumor specific responses after putting their DC-based immunotherapy apporach to the test in patients with renal cell carcinoma.Wednesday, June 28, 2017
iPSC-derived hepatocytes for drug identification and to study cellular pathophysiology
Cayo et al. have made an impressive work using new techniques such as iPSCs and humanized mice, to show that cardiac glycosides reduces hepatocyte production of apoB. They use apoB ELISA from Mabtech to analyze apoB secreted from iPSC-derived hepatocytes, and apoB in serum of avatar mice. They have also used the anti-apoB LDL17/20 for immunoprecipitation and Western Blot. Their article was published in April 2017 in the renowned journal Cell Stem Cell, and in the same edition, two other publications, Pashos et al. and Warren et al., are also analyzing secreted apoB from iPSC-derived hepatocytes using Mabtech’s apoB ELISA.
Liu et al. and Yang et al. are two additional recent papers studying inherited disorders with iPSC-derived hepatocytes, and like in the other articles, the authors are also using Mabtech’s apoB ELISA.Friday, June 16, 2017
Use of R848 and IL-2 to stimulate memory B cells
In 2013, Jahnmatz, M et al published a newly developed protocol for polyclonal activation of human memory B cells. The authors showed the superior functionality of stimulating B cells using the TLR7/8-agonist R848 and IL-2 compared to the other stimulation protocols used at the time. Since then, we include R848 and IL-2 in all of our human immunoglobulin ELISpot and FluoroSpot kits.
The article is now one of the most highly cited papers in Journal of Immunological Methods.Thursday, June 15, 2017
Characterization of Wilms’ tumor specific T cells with FluoroSpot
Danielzik et al. utilized Mabtech’s IFN-γ/Granzyme B FluroSpot kit to detect among others rare, specific, and double secreting T cells against Wilms’ tumor. The study honors high sensitivity, small sample size and the possibility to detect three different cell subsets in one FluoroSpot assay!Tuesday, June 13, 2017
IL-8 secretion in cattle after BoHV-4 infection
Premiere for our bovine IL-8 ELISA kit in the Reference-section. The study of Chanrot et al. demonstrates the susceptibility of bovine endometrial epithelial cells to bovine herpes virus 4 (BoHV-4), leading to increased IL-8 secretion. BoHV-4 is transmitted through breeding and is associated with abortion and chronic infertility in cows.Tuesday, May 30, 2017
CMV monitoring with IFN-gamma ELISpot
In addition, the assay proved to have low intra-assay, inter-assay, inter-operator and inter-site variability, and high linearity, sensitivity and specificity.Wednesday, May 24, 2017
Glycosylation differentiate latent TB from active
Look at this: Lu et al just published a paper in which they identify differential antibody glycosylation profiles that distinguish latent tuberculosis from active.Tuesday, September 27, 2016
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