Cancer Immunotherapy Review and Collection
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Cancer Immunotherapy Review and Collection
A magic life saving cure for advanced metastatic melanoma.  
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Ipilimumab (BMS) Review: A Cancer Breakthrough? - un knol de Krishan Maggon

Ipilimumab (BMS) Review: A Cancer Breakthrough? - un knol de Krishan Maggon | Cancer Immunotherapy Review and Collection | Scoop.it
FDA has approved Yervoy (ipilimumab, BMS) under REMS for the treatment of metastatic melanoma. The European expert panel CHMP...
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rosywills's comment, September 22, 2017 4:07 AM
Cancer Immunotherapy Market is expected to reach USD 119.39 Billion by 2021
Download Free Brochure @ http://bit.ly/2cHlrFH
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Researchers characterize mechanism of action of CAR T cells

Researchers characterize mechanism of action of CAR T cells | Cancer Immunotherapy Review and Collection | Scoop.it
The scientific community has made great strides over the past decade in the development of a new class of cancer therapy called immunotherapy, a treatment that activates a patient's own immune system to target cancer cells.
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Eagle and Mystic lead AstraZeneca’s cancer clear out  | FierceBiotech

Eagle and Mystic lead AstraZeneca’s cancer clear out  | FierceBiotech | Cancer Immunotherapy Review and Collection | Scoop.it
AstraZeneca has cleared a clutch of cancer programs from its clinical pipeline. The PD-L1 combination trials Eagle and Mystic led the clear out, and the immuno-oncology drugs tested in those studies feature heavily in the earlier-phase cull.
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Immune and genomic correlates of response to anti-PD-1 immunotherapy in glioblastoma

Immune and genomic correlates of response to anti-PD-1 immunotherapy in glioblastoma | Cancer Immunotherapy Review and Collection | Scoop.it
Genomic, transcriptomic, and microenvironmental analyses of samples from patients with glioblastoma treated with nivolumab or pembrolizumab identifies features associated with treatment response that may help in refining patient stratification.
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Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma

Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma | Cancer Immunotherapy Review and Collection | Scoop.it
Neoadjuvant pembrolizumab promotes a survival benefit with intratumoral and systemic immune responses in patients with recurrent glioblastoma.
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Engineering Nanoparticles for Targeted Remodeling of the Tumor Microenvironment to Improve Cancer Immunotherapy

Engineering Nanoparticles for Targeted Remodeling of the Tumor Microenvironment to Improve Cancer Immunotherapy | Cancer Immunotherapy Review and Collection | Scoop.it
Owing to the fast-paced growth and cross-infiltration of oncology, immunology and molecular biology, tumor immunotherapy technology represented by immune checkpoint blockade and chimeric antigen receptor (CAR) T cell therapy has lately made remarkable ...
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Inhibition of T cell activation and function by the adaptor protein CIN85

Inhibition of T cell activation and function by the adaptor protein CIN85 | Cancer Immunotherapy Review and Collection | Scoop.it
The ubiquitously expressed adaptor protein CIN85 has distinct roles in different cell types. This adaptor inhibits the activation of the receptor tyrosine kinases EGFR and PDGFR but promotes B cell receptor signaling. To determine its function in T cells, Kong et al. compared the activation of mouse T cells lacking CIN85 or the highly related adaptor CD2AP. Only loss of CIN85 augmented T cell growth and IL-2 production. CIN85 associated with the inhibitory phosphatase Sts-2 and promoted its recruitment to T cell receptor microclusters after activation. These data define a previously unknown inhibitory interaction, which could be targeted to augment T cell function in cancer and immunity.

T cell activation is initiated by signaling molecules downstream of the T cell receptor (TCR) that are organized by adaptor proteins. CIN85 (Cbl-interacting protein of 85 kDa) is one such adaptor protein. Here, we showed that CIN85 limited T cell responses to TCR stimulation. Compared to activated wild-type (WT) T cells, those that lacked CIN85 produced more IL-2 and exhibited greater proliferation. After stimulation of WT T cells with their cognate antigen, CIN85 was recruited to the TCR signaling complex. Early TCR signaling events, such as phosphorylation of ζ-chain–associated protein kinase 70 (Zap70), Src homology 2 (SH2) domain–containing leukocyte protein of 76 kDa (SLP76), and extracellular signal–regulated kinase (Erk), were enhanced in CIN85-deficient T cells. The inhibitory function of CIN85 required the SH3 and PR regions of the adaptor, which associated with the phosphatase suppressor of TCR signaling–2 (Sts-2) after TCR stimulation. Together, our data suggest that CIN85 is recruited to the TCR signaling complex and mediates inhibition of T cell activation through its association with Sts-2.
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Glioblastoma Immunotherapy Research at Penn Medicine, Including CART-EGFRvIII Therapy – Penn Medicine

Glioblastoma Immunotherapy Research at Penn Medicine, Including CART-EGFRvIII Therapy – Penn Medicine | Cancer Immunotherapy Review and Collection | Scoop.it
In collaboration with the dedicated Glioblastoma Translational Center of Excellence at the Abramson Cancer Center, investigators with the O’Rourke Laboratory in the Department of Neurosurgery are conducting research in immunotherapy for glioblastoma, including a currently enrolling clinical trial...
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Immunotherapy Drug Used As 1st-Line Therapy for Merkel Cell Carcinoma Improved Survival

Immunotherapy Drug Used As 1st-Line Therapy for Merkel Cell Carcinoma Improved Survival | Cancer Immunotherapy Review and Collection | Scoop.it
The fact that the incidence is highest in people who are immunosuppressed provides some support for the idea that Merkel cell carcinoma is an immunogenic cancer, one that is related to immune function, and a good candidate for immunotherapy. The National Cancer Institute defines immunotherapy as “a type of therapy that uses substances to stimulate or suppress the immune system to help the body fight cancer, infection, and other diseases. Some types of immunotherapy only target certain cells of the immune system. Others affect the immune system in a general way. Types of immunotherapy include cytokines, vaccines, bacillus Calmette-Guerin (BCG), and some monoclonal antibodies.” Pembrolizumab is a monoclonal antibody. Other centers participating in the trial are University of Washington/Fred Hutchinson Cancer Research Center, Johns Hopkins Kimmel Cancer Center and Bloomberg–Kimmel Institute for Cancer Immunotherapy, Emory University, Moffitt Cancer Center, Mount Sinai Medical Center, University of California San Francisco, Yale University, Stanford University, University of Pittsburgh, Duke University Medical Center, Ohio State University Comprehensive Cancer Center, City of Hope, Fred Hutchinson Cancer Research Center/Cancer Immunotherapy Trials Network, University of Washington, and Axio Research. The research was supported by grants from the National Cancer Institute, the Merkel cell carcinoma (MCC) patient gift fund at University of Washington, the Kelsey Dickson MCC Challenge Grant from the Prostate Cancer Foundation, the Al Copeland Foundation, and Merck, which provided pembrolizumab and partial funding for this study.
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Tumor-homing cytotoxic human induced neural stem cells for cancer therapy

Tumor-homing cytotoxic human induced neural stem cells for cancer therapy | Cancer Immunotherapy Review and Collection | Scoop.it
Healthy neural stem cells can infiltrate and help treat brain tumors because they naturally migrate toward gliomas in response to chemotactic signals released by the tumor cells. Obtaining neural stem cells from a patient can be difficult, however, and donor stem cells pose a risk of immune rejection and other safety concerns. Bagó et al . have discovered a way to avoid these risks by taking normal human skin fibroblasts and transdifferentiating them into neural stem cells. The entire process took only 4 days to complete, yielding autologous patient-derived neural stem cells. The authors engineered these stem cells to deliver two different types of therapies and demonstrated their ability to infiltrate and effectively treat brain tumors in multiple mouse models.

Engineered neural stem cells (NSCs) are a promising approach to treating glioblastoma (GBM). The ideal NSC drug carrier for clinical use should be easily isolated and autologous to avoid immune rejection. We transdifferentiated (TD) human fibroblasts into tumor-homing early-stage induced NSCs (h-iNSCTE), engineered them to express optical reporters and different therapeutic gene products, and assessed the tumor-homing migration and therapeutic efficacy of cytotoxic h-iNSCTE in patient-derived GBM models of surgical and nonsurgical disease. Molecular and functional analysis revealed that our single-factor SOX2 TD strategy converted human skin fibroblasts into h-iNSCTE that were nestin+ and expressed pathways associated with tumor-homing migration in 4 days. Time-lapse motion analysis showed that h-iNSCTE rapidly migrated to human GBM cells and penetrated human GBM spheroids, a process inhibited by blockade of CXCR4. Serial imaging showed that h-iNSCTE delivery of the proapoptotic agent tumor necrosis factor–α–related apoptosis-inducing ligand (TRAIL) reduced the size of solid human GBM xenografts 250-fold in 3 weeks and prolonged median survival from 22 to 49 days. Additionally, h-iNSCTE thymidine kinase/ganciclovir enzyme/prodrug therapy (h-iNSCTE–TK) reduced the size of patient-derived GBM xenografts 20-fold and extended survival from 32 to 62 days. Mimicking clinical NSC therapy, h-iNSCTE–TK therapy delivered into the postoperative surgical resection cavity delayed the regrowth of residual GBMs threefold and prolonged survival from 46 to 60 days. These results suggest that TD of human skin into h-iNSCTE is a platform for creating tumor-homing cytotoxic cell therapies for cancer, where the potential to avoid carrier rejection could maximize treatment durability in human trials.
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Our Engineered T-Cell Therapies :: Adaptimmune

Our Engineered T-Cell Therapies :: Adaptimmune | Cancer Immunotherapy Review and Collection | Scoop.it

By engineering the sequences that encode the T-cell receptors within a T-cell we can generate a T-cell therapy which works with a patient's own immune system to target specific cancer peptides. Our technology platform allows us to identify and select the T-cell receptors which are likely to prove the most effective in patients whilst minimising off-target (non-cancer cell) binding.

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Neutrophils escort circulating tumour cells to enable cell cycle progression

Neutrophils escort circulating tumour cells to enable cell cycle progression | Cancer Immunotherapy Review and Collection | Scoop.it
We use single-cell RNA sequencing to show that in the majority of these cases, CTCs were associated with neutrophils. When comparing the transcriptome profiles of CTCs associated with neutrophils against those of CTCs alone, we detect a number of differentially expressed genes that outline cell cycle progression, leading to more efficient metastasis formation. Further, we identify cell–cell junction and cytokine–receptor pairs that define CTC–neutrophil clusters, representing key vulnerabilities of the metastatic process. Thus, the association between neutrophils and CTCs drives cell cycle progression within the bloodstream and expands the metastatic potential of CTCs, providing a rationale for targeting this interaction in treatment of breast cancer.
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CD40: Targeting Co-Stimulatory Pathways for Cancer Immunotherapy

CD40: Targeting Co-Stimulatory Pathways for Cancer Immunotherapy | Cancer Immunotherapy Review and Collection | Scoop.it
Explore the role of CD40 in cancer immunotherapy, including background and functions, as well as why combination regimens may be key to targeting this checkpoint.
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Opdivo (nivolumab) Plus Yervoy (ipilimumab) Shows Response in Pre-Treated Patients with Metastatic Castration-Resistant Prostate Cancer | BMS Newsroom

Opdivo (nivolumab) Plus Yervoy (ipilimumab) Shows Response in Pre-Treated Patients with Metastatic Castration-Resistant Prostate Cancer | BMS Newsroom | Cancer Immunotherapy Review and Collection | Scoop.it
PRINCETON, N.J.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE: BMY) today announced data evaluating Opdivo (nivolumab) in combination with Yervoy (ipilimumab) in patients with metastatic castration-resistant prostate cancer (mCRPC).
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Vor Biopharma raises $42M in Series A round to advance AML cell therapy toward clinic

Vor Biopharma raises $42M in Series A round to advance AML cell therapy toward clinic | Cancer Immunotherapy Review and Collection | Scoop.it
5AM Ventures and RA Capital Management led the round. The company is developing hematopoietic stem cells engineered to be protected from targeted immunotherapies.
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Neoadjuvant nivolumab modifies the tumor immune microenvironment in resectable glioblastoma

Neoadjuvant nivolumab modifies the tumor immune microenvironment in resectable glioblastoma | Cancer Immunotherapy Review and Collection | Scoop.it
Neoadjuvant nivolumab treatment in patients with glioblastoma induces intratumoral immune activation and underscores the need for rationale-based combination approaches for improving clinical responses.
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Brain Cancer Breakthrough with Immunotherapy Points to New Hope for Patients

Brain Cancer Breakthrough with Immunotherapy Points to New Hope for Patients | Cancer Immunotherapy Review and Collection | Scoop.it
Giving Checkpoint Inhibitor Before Surgery Nearly Doubles Survival in Glioblastoma Patients, Says Study by PICI Researchers at UCLA A study from Parker Institute for Cancer Immunotherapy researchers at UCLA points to new hope for patients with recurrent glioblastoma, a type of brain cancer that...
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Blinatumomab versus Chemotherapy for Advanced Acute Lymphoblastic Leukemia | NEJM

Blinatumomab versus Chemotherapy for Advanced Acute Lymphoblastic Leukemia | NEJM | Cancer Immunotherapy Review and Collection | Scoop.it
Original Article from The New England Journal of Medicine — Blinatumomab versus Chemotherapy for Advanced Acute Lymphoblastic Leukemia...
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Glioblastoma Immunotherapy Research at Penn Medicine, Including CART-EGFRvIII Therapy – Penn Medicine

In collaboration with the dedicated Glioblastoma Translational Center of Excellence at the Abramson Cancer Center, investigators with the O’Rourke Laboratory in the Department of Neurosurgery are conducting research in immunotherapy for glioblastoma, including a currently enrolling clinical trial...
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Chimeric antigen receptor T cell targeting EGFRvIII for metastatic lung cancer therapy

Chimeric antigen receptor T cell targeting EGFRvIII for metastatic lung cancer therapy | Cancer Immunotherapy Review and Collection | Scoop.it
Abstract
Lung cancer is the most common incident cancer and the leading cause of cancer death. In recent years, the development of tumor immunotherapy especially chimeric antigen receptor T (CAR-T) cell has shown a promising future. Epidermal growth factor receptor variant III (EGFRvIII) is a tumor-specific mutation expressed in various types of tumors and has been detected in non-small cell lung cancer with a mutation rate of 10%. Thus, EGFRvIII is a potential antigen for targeted lung cancer therapy. In this study, CAR vectors were constructed and transfected into virus-packaging cells. Then, activated T cells were infected with retrovirus harvested from stable virus-producing single clone cell lines. CAR expression on the surfaces of the T cells was detected by flow cytometry andWestern blot. The function of CAR-T targeting EGFRvIII was then evaluated. The EGFRvIII-CAR vector was successfully constructed and confirmed by DNA sequencing. A stable virus-producing cell line was produced from a single clone by limited dilution. The culture conditions for the cell line, including cell density, temperature, and culture medium were optimized. After infection with retrovirus, CAR was expressed on more than 90% of the T cells. The proliferation of CAR-T cells were induced by cytokine and specific antigen in vitro. More importantly, EGFRvIII-CART specifically and efficiently recognized and killed A549-EGFRvIII cells with an effector/target ratio of 10:1 by expressing and releasing cytokines, including perforin, granzyme B, IFN-g, and TNF-α. The in vivo study indicated that the metastasis of A549-EGFRvIII cells in mice were inhibited by EGFRvIII-CART cells, and the survival of the mice was significantly prolonged with no serious side effects. EGFRvIII-CART showed significantly efficient antitumor activity against lung cancer cells expressing EGFRvIII in vivo and in vitro. Therefore, CAR-T targeting EGFRvIII is a potential therapeutic strategy in preventing recurrence and metastasis of lung cancer after surgery.

Keywords
chimeric antigen receptor T cells epidermal growth factor receptor lung cancer immunotherapy tumor immunology 
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Development of tumor mutation burden as an immunotherapy biomarker: utility for the oncology clinic | Annals of Oncology | Oxford Academic

Development of tumor mutation burden as an immunotherapy biomarker: utility for the oncology clinic | Annals of Oncology | Oxford Academic | Cancer Immunotherapy Review and Collection | Scoop.it
Abstract
Background
Treatment with immune checkpoint blockade (ICB) with agents such as anti-programmed cell death protein 1 (PD-1), anti-programmed death-ligand 1 (PD-L1), and/or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) can result in impressive response rates and durable disease remission but only in a subset of patients with cancer. Expression of PD-L1 has demonstrated utility in selecting patients for response to ICB and has proven to be an important biomarker for patient selection. Tumor mutation burden (TMB) is emerging as a potential biomarker. However, refinement of interpretation and contextualization is required.

Materials and methods
In this review, we outline the evolution of TMB as a biomarker in oncology, delineate how TMB can be applied in the clinic, discuss current limitations as a diagnostic test, and highlight mechanistic insights unveiled by the study of TMB. We review available data to date studying TMB as a biomarker for response to ICB by tumor type, focusing on studies proposing a threshold for TMB as a predictive biomarker for ICB activity.

Results
High TMB consistently selects for benefit with ICB therapy. In lung, bladder and head and neck cancers, the current predictive TMB thresholds proposed approximate 200 non-synonymous somatic mutations by whole exome sequencing (WES). PD-L1 expression influences response to ICB in high TMB tumors with single agent PD-(L)1 antibodies; however, response may not be dependent on PD-L1 expression in the setting of anti-CTLA4 or anti-PD-1/CTLA-4 combination therapy. Disease-specific TMB thresholds for effective prediction of response in various other malignancies are not well established.

Conclusions
TMB, in concert with PD-L1 expression, has been demonstrated to be a useful biomarker for ICB selection across some cancer types; however, further prospective validation studies are required. TMB determination by selected targeted panels has been correlated with WES. Calibration and harmonization will be required for optimal utility and alignment across all platforms currently used internationally. Key challenges will need to be addressed before broader use in different tumor types.

mutation, immunotherapy, immune checkpoint, cancer
Topic: mutation cancer biological markers immunotherapy medical oncology neoplasms mutation, somatic cell cycle checkpoint whole exome sequencing programmed cell death 1 ligand 1
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Clinical implications of tumor-intrinsic mechanisms regulating PD-L1

Clinical implications of tumor-intrinsic mechanisms regulating PD-L1 | Cancer Immunotherapy Review and Collection | Scoop.it
Treatment with immune checkpoint inhibitors targeting programmed death receptor-1 (PD-1) or programmed death ligand-1 (PD-L1) is effective in many cancer types. Tumors harboring specific mutations modulate antitumor immune responses through the PD-1/PD-L1 axis, and this should be taken into account when designing rational combinatory treatments.
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Torque and Thermo Fisher Scientific Announce Collaboration to Build State-of-the-Art Facility to Manufacture Torque’s Deep-Primed T Cell Immunotherapies

Torque and Thermo Fisher Scientific Announce Collaboration to Build State-of-the-Art Facility to Manufacture Torque’s Deep-Primed T Cell Immunotherapies | Cancer Immunotherapy Review and Collection | Scoop.it
Torque & Thermo Fisher Scientific to Build State-of-the-Art Facility to Manufacture Deep-Primed T Cell Immunotherapies...
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Anti-tumour immunity controlled through mRNA m 6 A methylation and YTHDF1 in dendritic cells

Anti-tumour immunity controlled through mRNA m 6 A methylation and YTHDF1 in dendritic cells | Cancer Immunotherapy Review and Collection | Scoop.it
There is growing evidence that tumour neoantigens have important roles in generating spontaneous antitumour immune responses and predicting clinical responses to immunotherapies1,2. Despite the presence of numerous neoantigens in patients, complete tumour elimination is rare, owing to failures in mounting a sufficient and lasting antitumour immune response3,4. Here we show that durable neoantigen-specific immunity is regulated by mRNA N6-methyadenosine (m6A) methylation through the m6A-binding protein YTHDF15. In contrast to wild-type mice, Ythdf1-deficient mice show an elevated antigen-specific CD8+ T cell antitumour response. Loss of YTHDF1 in classical dendritic cells enhanced the cross-presentation of tumour antigens and the cross-priming of CD8+ T cells in vivo. Mechanistically, transcripts encoding lysosomal proteases are marked by m6A and recognized by YTHDF1. Binding of YTHDF1 to these transcripts increases the translation of lysosomal cathepsins in dendritic cells, and inhibition of cathepsins markedly enhances cross-presentation of wild-type dendritic cells. Furthermore, the therapeutic efficacy of PD-L1 checkpoint blockade is enhanced in Ythdf1−/− mice, implicating YTHDF1 as a potential therapeutic target in anticancer immunotherapy.
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New ACCC report helps incorporate cancer immunotherapies into practice

New ACCC report helps incorporate cancer immunotherapies into practice | Cancer Immunotherapy Review and Collection | Scoop.it
New ACCC report helps incorporate cancer immunotherapies into practice...
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