654 Personalised tumour-trained lymphocytes derived from regional lymph nodes for treatment of colorectal cancer (original) (raw)
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Revolutionizing Cancer Therapy with Newer Treatment Modalities: A Review
Saudi Journal of Medical and Pharmaceutical Sciences, 2020
Non communicable diseases like Cancer is a leading cause of death group worldwide. The reason for every sixth death in the world is cancer, making it the second leading cause of death. Curing cancer is certainly one of the biggest challenges of the 21st century. In the last two decades, our knowledge of cancer and its treatment has greatly improved. This has revealed the huge variability that can be found between not only different types of cancer, but also between patients with the same type of cancer. It seems increasingly evident that there won't be a single method to ‗cure' rather, each patient will be treated accordingly to their specific needs. But for individualized medicine to become a reality, we need a range of therapies wide enough to cover the broad spectrum of cancer. It has been found that cancer in one person doesn't always behave the same way in another person. Thanks to the innovative research that has fueled the newer treatment options available for cancer treatment that increases the individuals' survival rate. New approaches to cultivate the immune system in the fight against cancer are getting us closer to a future where cancer becomes a curable disease. Targeted therapies, personalized vaccines, gene therapy, microbiome treatments and stem cell transplantation are some of the technologies that will change the way of cancer treatment.
[Trends in oncological phase I trials]
2019
This review summarises the current knowledge of anticancer therapy. More than 1,100 cancer drugs are currently under development in the United States. The increasing biological insight and platforms for high throughput screening of drugs have changed the developmental landscape of anticancer therapies from classical cytotoxic agents to targeted agents and immunotherapy. There is an increasing number of targeted agents, which are only efficacious in tumours harbouring specific genomic alterations in early clinical development. Furthermore, the landscape of immunotherapy broadens, and personalised immunotherapy is in development. The integration of genomic testing into early clinical oncology trials is increasing.
An overview on cell-based therapy: Unique perspective for cancer management
Asian Journal of Pharmacy and Pharmacology
Cell-based immunotherapy is currently one of the most exciting developments in the fight against cancer, and to date, cellular therapies have been approved for people with certain blood cancers, but the cell therapy for solid tumors has yet to achieve that same milestone. Solid tumors comprise about 90% of all cancer diagnoses, thereby indicating more research on cell therapy technology as well as scalable production that could expand this treatment to the larger number of people with cancer. Cell therapy uses the living cells as a drug to treat disease, and when used to treat cancer, cell therapy takes advantage of the immune system's intrinsic ability to seek out and destroy abnormal cells in the body. Developing cell therapies to attack cancer cells for solid tumors, to persist in the body and overcome tumor's ability to hide from the immune system, has been notoriously difficult. With the technologies available, cell therapy is very expensive and difficult to produce in scalable quantities.
Cancer Biotherapy and Radiopharmaceuticals, 2003
The Cancer Biotherapy Research Group conducted a clinical trial to verify encouraging reports of antitumor activity of autolymphocyte therapy. Patients and Methods: Patients with a variety of advanced solid malignancies underwent an initial leukapheresis procedure to collect about 5 3 10 9 autologous lymphocytes that were stimulated in vitro for 3 days with anti-CD3 monoclonal antibody in the presence of indomethicin and cis-retinoic acid to obtain media that was frozen in aliquots. This media contained significant amounts of tumor necrosis factor (TNF)-a, interleukin (IL)-1b, interferon-g, and IL-6, but no IL-2. Subsequently patients underwent up to 6 monthly leukaphereses to collect 2-5 3 10 9 autologous lymphocytes that were incubated in vitro for 6 days in the cryopreserved media containing autologous lymphokines, resulting in a cell population enriched for noncytotoxic T-helper lymphocytes. These were administered intravenously monthly for up to 6 months with daily oral cimetidine at a dose of 600 mg po qid, which was given throughout the treatment period. Tumor response was assessed every 2 months. Results: There were 47 patients (25 women and 22 men) with a median age of 55 years (range 31-79). One hundred seventy four treatments were delivered and were well tolerated. A mean of 2.05 6 1.46 (range 0.82-12.8 3 10 9) cells were infused. Eighty-five percent received two or more doses; 19% received six doses. Objective tumor responses were observed in 1/15 renal cell, 1/13 colorectal, 0/6 breast, 0/5 lung, 0/2 gastric, 0/2 sarcoma, 0/1 pancreas, 0/1 prostate, 0/1 melanoma, and 0/1 eccrine. Forty-three patients have died. Median survival was 8.8 months, 1-year survival 35%, and 2-year survival 15%. Conclusion: This complex treatment program was feasible. Infusion of these cells was well tolerated. Some antitumor activity was seen in patients with renal cell cancer and colorectal cancer.
New_Approaches_for_Cancer_Therapy_2016_12_02_08_35_02_801.pdf
Summary Cancer which represents a group of unprecedented heterogeneous diseases that affects humans with high morbidity and mortality was once thought as a single disease; but now with the advance in molecular and genetic bases of cancer it consists of a large number of different conditions in all its form that changes the genetic blueprint of the organism that finally leads to uncontrolled cell division and progression. The onset of cancer (carcinogenesis) is usually initiated with DNA alteration in the target cell that mostly arises as a result of a combination of several factors including genetics, environment, and diet, immune as well as several others still under investigations and to be discovered. The genetic blue print alternation may include a single point nucleotide exchange, deletion, amplification, translocation, chromosomal rearrangement that leads to the activation of oncognes and suppression of tumor suppressor genes. In addition to genetic abnormality of cancer related genes epigenetic control of genes (change of gene expression pattern mediated by modification of DNA without direct alteration of nucleotide sequences of the gene) also plays a significant role in the process of cancer development. The treatment modalities and therapeutic agents currently available for the diseases are surgery, radiotherapy and chemotherapy which mainly focus on palliative and preventive or prophylaxis for the disease. But treatments for advanced stage cancer are often difficult with a limited efficacy despite multimodal therapeutic strategies. Novel approaches are required to improve or cure the disease with a molecular targeting small sized synthetic chemical substance like monoclonal antibody, different vaccines anti-sense oligonucleotides and hormones. Some of these agents are currently available and furthermore many candidates are under clinical investigations. Gene therapy is also a possible treatment modality and over the past decades has been tested pre-clinically and clinically for its feasibility in different parts of the world but none of the gene medicine has yet been approved by FDA for clinical use except one drug known as Gendicine which is approved by Chinese Food and Drug Administration for the treatment of head and neck cancer.
Journal for ImmunoTherapy of Cancer
BackgroundOX40 is a costimulatory receptor upregulated on antigen-activated T cells and constitutively expressed on regulatory T cells (Tregs). INCAGN01949, a fully human immunoglobulin G1κ anti-OX40 agonist monoclonal antibody, was designed to promote tumor-specific immunity by effector T-cell activation and Fcγ receptor-mediated Treg depletion. This first-in-human study was conducted to determine the safety, tolerability, and preliminary efficacy of INCAGN01949.MethodsPhase I/II, open-label, non-randomized, dose-escalation and dose-expansion study conducted in patients with advanced or metastatic solid tumors. Patients received INCAGN01949 monotherapy (7–1400 mg) in 14-day cycles while deriving benefit. Safety measures, clinical activity, pharmacokinetics, and pharmacodynamic effects were assessed and summarized with descriptive statistics.ResultsEighty-seven patients were enrolled; most common tumor types were colorectal (17.2%), ovarian (8.0%), and non-small cell lung (6.9%) can...
Stepping Stones Toward Cancer Immunotherapy
Journal of Immunotherapy, 2005
Cancer and many other serious diseases are characterized by the uncontrolled growth of new blood vessels. Recently, RNA interference (RNAi) has reinvigorated the therapeutic prospects for inhibiting gene expression and promises many advantages over binding inhibitors, including high specificity, which is essential for targeted therapeutics. The modulation of angiogenesis pathways using small interfering RNA (siRNA) inhibitors of gene expression has proven to be a powerful approach which would be applied for treatment of multiple cancers. Using a nanoparticle-mediated systemic delivery of siRNA with a dual targeting specificity to both neovasculature and VEGF receptor 2 (KDR), we were able to achieve anti-tumor efficacies in multiple tumor models. We further tested this potential anticancer drug candidate, ICS-283, in combination with Genentech's Avastin, a mAb against VEGF A in colorectal tumor cell DLD-1 xenograft model. The combined regimen resulted stronger anticancer efficacy than either of the component alone with significant evidence of anti-angiogenesis activities. We will report the latest results of this novel approach, further discuss the underlined mechanism action of this mAb-siRNA combination for potent anti-angiogenesis therapy and its clinical implication for cancer treatment. The dual-targeted therapeutics and the combination of siRNAs targeting multiple pro-angiogenesis factors have further demonstrated the advantages of this novel therapeutic modality. As with any emerging technologies, many issues related to siRNA therapeutics must be addressed diligently before the success of this novel approach can be achieved in clinics.
Recent Developments in Cancer Treatment: A Review
Pharmaceutical Regulatory Affairs: Open Access, 2014
According to the latest cancer statistics presented worldwide, there has been a dramatic increase in the rates of occurrence of some cancers, particularly in the more developed countries. Although many therapeutic strategies to prevent and/or cure this disease have been proposed and evaluated by clinicians and researchers, there remains a need to find more effective approaches. Side effects such as toxicity and drug resistance are two of the most frequent problems faced during chemotherapy. Small-molecule drugs are being intensively pursued as new anticancer therapeutics. Oncology drug discovery has benefited significantly from progress in understanding how to target kinases with small molecules that were found to be correlated with the disease. One reason for this is that many kinases have been found to be intimately involved in the processes leading to tumor cell proliferation and survival. Monoclonal antibodies, that are produced in vitro, can be used in cancer treatment in a number of ways. They may enhance the immune system by reacting with certain types of cancer cells. They can be programmed to act against specific cell growth factors to interfere with the growth of cancer cells. Furthermore, they may be linked to anticancer drugs, radioactive substances, other biologic therapies, or other toxins (antibody-drug conjugates). Finally, the usage of cytotoxic monoclonal antibodies during the process of bone marrow transplantation may be a key to improve the efficacy of the method.