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Adoptive immunotherapy

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https://www.readbyqxmd.com/read/28434148/advancing-chimeric-antigen-receptor-t-cell-therapy-with-crispr-cas9
#1
REVIEW
Jiangtao Ren, Yangbing Zhao
The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (CRISPR/Cas9) system, an RNA-guided DNA targeting technology, is triggering a revolution in the field of biology. CRISPR/Cas9 has demonstrated great potential for genetic manipulation. In this review, we discuss the current development of CRISPR/Cas9 technologies for therapeutic applications, especially chimeric antigen receptor (CAR) T cell-based adoptive immunotherapy. Different methods used to facilitate efficient CRISPR delivery and gene editing in T cells are compared...
April 22, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28430646/immunotherapeutic-target-expression-on-breast-tumors-can-be-amplified-by-hormone-receptor-antagonism-a-novel-strategy-for-enhancing-efficacy-of-targeted-immunotherapy
#2
Ritika Jaini, Matthew G Loya, Charis Eng
Immunotherapy has historically been successful in highly antigenic tumors but has shown limited therapeutic efficacy in non-antigenic tumors such as breast cancers. Our previous studies in autoimmunity have demonstrated that increased antigen load within a tissue enhances immune reactivity against it. We therefore hypothesized that enhancing expression of target proteins on breast tumors can increase efficacy of targeted immunotherapy. We hypothesized that antagonism of the estrogen receptor (ER) can increase expression of targets that are hormonally regulated and facilitate enhanced tumor recognition by targeted immunotherapy...
March 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28429069/mupexi-prediction-of-neo-epitopes-from-tumor-sequencing-data
#3
Anne-Mette Bjerregaard, Morten Nielsen, Sine Reker Hadrup, Zoltan Szallasi, Aron Charles Eklund
Personalization of immunotherapies such as cancer vaccines and adoptive T cell therapy depends on identification of patient-specific neo-epitopes that can be specifically targeted. MuPeXI, the mutant peptide extractor and informer, is a program to identify tumor-specific peptides and assess their potential to be neo-epitopes. The program input is a file with somatic mutation calls, a list of HLA types, and optionally a gene expression profile. The output is a table with all tumor-specific peptides derived from nucleotide substitutions, insertions, and deletions, along with comprehensive annotation, including HLA binding and similarity to normal peptides...
April 20, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28428503/-cancer-immunotherapy-utilizing-t-cell-receptor-gene-engineering
#4
Hiroaki Ikeda
Immune-checkpoint inhibitors have shown their efficacy in the treatment of patients with many kinds of progressive/relapsed cancers. However, the efficacy remains as 10-40%of the patients in most type of cancers, suggesting that the development of new therapy for patients resistant to the therapy is an urgent unmet need. Adoptive therapy with tumor-specific T cells is a promising therapy that can be effective in patients who are not benefited from the immune-checkpoint inhibitors. The T cell therapy with genetic engineering in T cell receptor(TCR)is expected to be a universal therapy because this therapy can be applicable for patients with many kinds of cancers...
April 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28426690/phenotypic-characterization-and-anticancer-capacity-of-cd8-cytokine-induced-killer-cells-after-antigen-induced-expansion
#5
Jianhua Liu, Lu Wang, Yaoling Wang, Wenjie Zhang, Yilin Cao
Cytokine-induced killer cells (CIK) have been used in clinic for adoptive immunotherapy in a variety of malignant tumors and have improved the prognosis of cancer patients. However, there are individual differences in the CIK cell preparations including the obvious differences in the ratio of effector CIK cells among different cancer patients. Infusion of such heterogeneous immune cell preparation is an important factor that would affect the therapeutic efficacy. We report here the enrichment and expansion of CD8+ cells from CIK cells cultured for one week using magnetic activated cell sorting (MACS)...
2017: PloS One
https://www.readbyqxmd.com/read/28424328/toward-off-the-shelf-adoptive-t-cell-therapies
#6
Kwanghun Chung
Artificial thymic organoids may enable more efficient engineered T cell production for immunotherapy.
April 19, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28423454/uk-neqas-survey-of-allergen-component-testing-across-the-united-kingdom-and-other-european-countries
#7
R Saleem, C Keymer, D Patel, W Egner, A W Rowbottom
The clinical utility of molecular diagnostic approaches in allergy investigation is being recognized increasingly to play a significant role in the management of allergic patients. Determining the sensitization pattern, which is best achieved through the use of component resolved diagnostics (CRD), allows effective risk stratification, appropriate treatment and patient selection for immunotherapy. In order to assess the diagnostic service provisions for in-vitro allergy testing across Europe, a survey was carried out via the total immunoglobulin (Ig)E and specific IgE external quality assurance schemes run by UK National External Quality Assessment Service (NEQAS) Immunology, Immunochemistry and Allergy...
April 19, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28422742/multi-omics-study-revealing-the-complexity-and-spatial-heterogeneity-of-tumor-infiltrating-lymphocytes-in-primary-liver-carcinoma
#8
Lijun Shi, Yang Zhang, Lin Feng, Liming Wang, Weiqi Rong, Fan Wu, Jianxiong Wu, Kaitai Zhang, Shujun Cheng
Intratumoral heterogeneity has been revealed in primary liver carcinoma (PLC). However, spatial heterogeneity of tumor-infiltrating lymphocytes (TILs), which reflects one dimension of a tumor's spatial heterogeneity, and the relationship between TIL diversity, local immune response and mutation burden remain unexplored in PLC. Therefore, we performed immune repertoire sequencing, gene expression profiling analysis and whole-exome sequencing in parallel on five regions of each tumor and on matched adjacent normal tissues and peripheral blood from five PLC patients...
March 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418996/mobilizing-immune-cells-with-exercise-for-cancer-immunotherapy
#9
Richard J Simpson, Austin B Bigley, Nadia Agha, Patrick J Hanley, Catherine M Bollard
Hematopoietic stem cell (HSC) transplantation and adoptive transfer immunotherapy are effective in treating blood cancers and post-transplant infections, but low circulating cell numbers in patients and donors is oftentimes a limiting factor. We postulate that a single exercise bout will increase the yield of patient and donor-derived HSC's and cytotoxic lymphocytes to improve this form of treatment for cancer patients.
April 17, 2017: Exercise and Sport Sciences Reviews
https://www.readbyqxmd.com/read/28414151/targeted-antigen-delivery-to-dendritic-cell-via-functionalized-alginate-nanoparticles-for-cancer-immunotherapy
#10
Chuangnian Zhang, Gaona Shi, Ju Zhang, Huijun Song, Jinfeng Niu, Shengbin Shi, Pingsheng Huang, Yanming Wang, Weiwei Wang, Chen Li, Deling Kong
The purpose of the present study was to identify an "easy-to-adopt" strategy to enhance immune responses using functionalized alginate (ALG) nanoparticles (MAN-ALG/ALG=OVA NPs), which were prepared by CaCl2 cross-linking of two different types of ALG. The mannose (MAN) modified ALG (MAN-ALG) was used for dendritic cell targeting. The other component, composed of ovalbumin (OVA), a model antigen, is conjugated to ALG (ALG=OVA) via pH sensitive Schiff base bond. Grafting of alginate was demonstrated by FT-IR and (1)H NMR, while the morphological structure, particle size, Zeta potential of MAN-ALG/ALG=OVA NPs were measured using TEM and DLS...
April 13, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28410302/tumor-infiltrating-lymphocyte-therapy-and-neoantigens
#11
Paul F Robbins
The adoptive cell transfer (ACT) of autologous tumor-infiltrating lymphocytes has been shown to be effective at mediating tumor regression in more than half of patients with metastatic melanoma and in mediating long-term complete regression in approximately one fourth of all patients with this cancer. The success of this approach in patients with cholangiocarcinoma and colon cancer supports efforts to expand ACT therapies to treatment of patients bearing a wide array of cancer types. Recent improvements in deep sequencing of the patient cancers, combined with extensive immunological testing of autologous tumor-infiltrating lymphocytes, indicate that T cells targeting epitopes arising from nonsynonymous somatic mutations, termed neoantigens, play important roles in mediating many of the effective cancer immunotherapies seen in response to ACT...
March 2017: Cancer Journal
https://www.readbyqxmd.com/read/28410299/antigen-discovery-and-therapeutic-targeting-in-hematologic-malignancies
#12
David A Braun, Catherine J Wu
Historically, immune-based therapies have played a leading role in the treatment of hematologic malignancies, with the efficacy of stem cell transplantation largely attributable to donor immunity against malignant cells. As new and more targeted immunotherapies have developed, their role in the treatment of hematologic malignancies is evolving and expanding. Herein, we discuss approaches for antigen discovery and review known and novel tumor antigens in hematologic malignancies. We further explore the role of established and investigational immunotherapies in hematologic malignancies, with a focus on personalization of treatment modalities such as cancer vaccines and adoptive cell therapy...
March 2017: Cancer Journal
https://www.readbyqxmd.com/read/28408606/landscape-of-immunogenic-tumor-antigens-in-successful-immunotherapy-of-virally-induced-epithelial-cancer
#13
Sanja Stevanović, Anna Pasetto, Sarah R Helman, Jared J Gartner, Todd D Prickett, Bryan Howie, Harlan S Robins, Paul F Robbins, Christopher A Klebanoff, Steven A Rosenberg, Christian S Hinrichs
Immunotherapy has clinical activity in certain virally associated cancers. However, the tumor antigens targeted in successful treatments remain poorly defined. We used a personalized immunogenomic approach to elucidate the global landscape of antitumor T cell responses in complete regression of human papillomavirus-associated metastatic cervical cancer after tumor-infiltrating adoptive T cell therapy. Remarkably, immunodominant T cell reactivities were directed against mutated neoantigens or a cancer germline antigen, rather than canonical viral antigens...
April 14, 2017: Science
https://www.readbyqxmd.com/read/28405474/rheumatic-immune-related-adverse-events-of-checkpoint-therapy-for-cancer-case-series-of-a-new-nosological-entity
#14
C Calabrese, E Kirchner, K Kontzias, V Velcheti, L H Calabrese
Immunotherapy of cancer with checkpoint inhibitors has been associated with a spectrum of autoimmune and systemic inflammatory reactions known as immune-related adverse events (irAEs). Rheumatic irAEs are infrequently reported and extensively described. Here, we report our experience over an 18-month period with 15 patients evaluated in the rheumatology department for rheumatic irAEs. We identified 13 patients without pre-existing autoimmune disease (AID) who subsequently developed rheumatic irAEs, and two with established AID referred pre-emptively...
2017: RMD Open
https://www.readbyqxmd.com/read/28405194/modeling-natural-killer-cell-targeted-immunotherapies
#15
REVIEW
Silvia Lopez-Lastra, James P Di Santo
Animal models have extensively contributed to our understanding of human immunobiology and to uncover the underlying pathological mechanisms occurring in the development of diseases. However, mouse models do not reproduce the genetic and molecular complexity inherent in human disease conditions. Human immune system (HIS) mouse models that are susceptible to human pathogens and can recapitulate human hematopoiesis and tumor immunobiology provide one means to bridge the interspecies gap. Natural killer cells are the founding member of the innate lymphoid cell family...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28396751/an-abscopal-effect-in-a-case-of-concomitant-treatment-of-locally-and-peritoneally-recurrent-gastric-cancer-using-adoptive-t-cell-immunotherapy-and-radiotherapy
#16
Hiro Sato, Yoshiyuki Suzuki, Yuya Yoshimoto, Shin-Ei Noda, Kazutoshi Murata, Yosuke Takakusagi, Atsushi Okazaki, Tetsuo Sekihara, Takashi Nakano
The mechanism of abscopal effect is becoming clear by the progress of cancer immunology. A 54-year-old male with recurrent gastric cancer presented an abscopal effect after radiotherapy with concurrent adoptive T-cell immunotherapy (immunoradiotherapy). Immunoradiotherapy has potential to induce abscopal effect by strengthening systemic antitumor immunity even in recurrent cancer.
April 2017: Clinical Case Reports
https://www.readbyqxmd.com/read/28395881/adopting-a-new-stance-on-immunotherapy-for-uveal-melanoma
#17
Kimberly M Komatsubara, Richard D Carvajal
No abstract text is available yet for this article.
April 7, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28395880/treatment-of-metastatic-uveal-melanoma-with-adoptive-transfer-of-tumour-infiltrating-lymphocytes-a-single-centre-two-stage-single-arm-phase-2-study
#18
Smita S Chandran, Robert P T Somerville, James C Yang, Richard M Sherry, Christopher A Klebanoff, Stephanie L Goff, John R Wunderlich, David N Danforth, Daniel Zlott, Biman C Paria, Arvind C Sabesan, Abhishek K Srivastava, Liqiang Xi, Trinh H Pham, Mark Raffeld, Donald E White, Mary Ann Toomey, Steven A Rosenberg, Udai S Kammula
BACKGROUND: Uveal melanoma is a rare tumour with no established treatments once metastases develop. Although a variety of immune-based therapies have shown efficacy in metastatic cutaneous melanoma, their use in ocular variants has been disappointing. Recently, adoptive T-cell therapy has shown salvage responses in multiple refractory solid tumours. Thus, we sought to determine if adoptive transfer of autologous tumour-infiltrating lymphocytes (TILs) could mediate regression of metastatic uveal melanoma...
April 7, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28386262/preservation-of-antigen-specific-functions-of-%C3%AE-%C3%AE-t-cells-and-b-cells-removed-from-hematopoietic-stem-cell-transplants-suggests-their-use-as-an-alternative-cell-source-for-advanced-manipulation-and-adoptive-immunotherapy
#19
Giuseppina Li Pira, Stefano Di Cecca, Simone Biagini, Elia Girolami, Elisabetta Cicchetti, Valentina Bertaina, Concetta Quintarelli, Ignazio Caruana, Barbarella Lucarelli, Pietro Merli, Daria Pagliara, Letizia Pomponia Brescia, Alice Bertaina, Mauro Montanari, Franco Locatelli
Hematopoietic stem cell transplantation is standard therapy for numerous hematological diseases. The use of haploidentical donors, sharing half of the HLA alleles with the recipient, has facilitated the use of this procedure as patients can rely on availability of a haploidentical donor within their family. Since HLA disparity increases the risk of graft-versus-host disease, T-cell depletion has been used to remove alloreactive lymphocytes from the graft. Selective removal of αβ T cells, which encompass the alloreactive repertoire, combined with removal of B cells to prevent EBV-related lymphoproliferative disease, proved safe and effective in clinical studies...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28383769/unleashing-the-immune-response-against-childhood-solid-cancers
#20
REVIEW
John Anderson
Tumor immunotherapy has come to the fore fuelled by impressive clinical responses to checkpoint inhibitor antibodies in a range of adult malignancies and by the success of chimeric antigen receptor T cells targeting adult and pediatric B-cell malignancies. Clearly, if appropriately fine-tuned, the immune system has the capability to seek out and destroy cancer. Studies in pediatric solid cancers so far have not shown the therapeutic potential checkpoint inhibitors described in adult cancers and this may reflect fewer tumor-associated antigens or different immune evasion mechanisms...
April 6, 2017: Pediatric Blood & Cancer
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