癌症免疫療法的前世今生

相關論文信息

一

【論文作者】ChristopherR Parish

【發表時間】2002年12月24日

【發表期刊】Nature

【論文鏈接】https://www.nature.com/articles/icb200316

【論文編號】doi:10.1046/j.0818-9641.2003.01151.x

【論文摘要】One of the mostcontroversial issues in immunology for over a century has been whether aneffective immune response can be elicited against malignant tumours. Whetherthe immunology community has believed cancer immunotherapy is feasible orimpossible has been largely determined by the prevailing immunologicalparadigms at that time. In fact, during the last 110 years it is possible totrace at least five dramatic fluctuations in attitude towards cancer immunotherapy.It now appears, however, that overwhelming evidence is available to support theview that both the innate and adaptive immune responses can recognize andeliminate tumours. On the other hand, it remains to be seen if these immuneresponses can be harnessed to control cancer as, at the time of diagnosis, manytumours have already been immunoselected to be highly resistant to immuneelimination. Based on these observations it is argued that immunotherapyapproaches, other than the generation of tumour-specific cytotoxi c Tlymphocytes, must be explored. Alternative strategies include recruitingtumouricidal myeloid cells into tumours, generating antiangiogenic immuneresponses and directing innate immunity to hypoxia-induced ligands on tumourcells.

二

【論文作者】EdwardF McCarthy

【發表時間】2006年

【發表期刊】IowaOrthop J. 2006; 26: 154–158.

【論文鏈接】https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1888599/

【論文編號】PMC1888599

【論文摘要】In1891, William B. Coley injected streptococcal organisms into a patient withinoperable cancer. He thought that the infection he produced would have theside effect of shrinking the malignant tumor. He was successful, and this wasone of the first examples of immunotherapy. Over the next forty years, as headof the Bone Tumor Service at Memorial Hospital in New York, Coley injected morethan 1000 cancer patients with bacteria or bacterial products. These productsbecame known as Coley’s Toxins. He and other doctors who used them reportedexcellent results, especially in bone and soft-tissue sarcomas.

Despite his reported goodresults, Coley’s Toxins came under a great deal of criticism because manydoctors did not believe his results. This criticism, along with the developmentof radiation therapy and chemotherapy, caused Coley’s Toxins to graduallydisappear from use. However, the modern science of immunology has shown thatColey’s principles were correct and that some cancers are sensitive to an enhancedimmune system. Because research is very active in this field, William B. Coley,a bone sarcoma surgeon, deserves the title “Father of Immunotherapy.”

三

【論文標題】Individualizedvaccination of AML patients in remission is associated with induction ofantileukemia immunity and prolonged remissions

【論文作者】JacalynRosenblatt, Richard M. Stone, et al.

【發表時間】2016年12月7日

【發表期刊】ScienceTranslational Medicine

【論文鏈接】

http://stm.sciencemag.org/content/8/368/368ra171

【論文編號】DOI:10.1126/scitranslmed.aag1298

【論文摘要】We developed a personalized cancer vaccine in whichpatient-derived acute myeloid leukemia (AML) cells are fused with autologousdendritic cells, generating a hybridoma that potently stimulates broadantitumor responses. We report results obtained from the first 17 AML patients,who achieved remission after chemotherapy and were then serially vaccinated totarget minimal residual disease and prevent relapse. Vaccination was welltolerated and induced inflammatory responses at the site of administration,characterized by the dense infiltration of T cells. Vaccination was alsoassociated with a marked rise in circulating T cells recognizing whole AMLcells and leukemia-specific antigens that persisted for more than 6 months.Twelve of 17 vaccinated patients (71%; 90% confidence interval, 52 to 89%)remain alive without recurrence at a median follow-up of 57 months. The resultsdemonstrate that personalized vaccination of AML patients in remission inducesthe expansion of leukemia-sp ecific T cells and may be protective againstdisease relapse.

四

【論文標題】Eradication of spontaneous malignancy by localimmunotherapy

【論文作者】Ronald Levy, Idit Sagiv-Barfi, et al.

【發表時間】2018年1月31日

【發表期刊】ScienceTranslational Medicine

【論文鏈接】http://stm.sciencemag.org/content/10/426/eaan4488

【論文編號】DOI:10.1126/scitranslmed.aan4488

【論文摘要】It has recently become apparent that the immune systemcan cure cancer. In some of these strategies, the antigen targets arepreidentified and therapies are custom-made against these targets. In others,antibodies are used to remove the brakes of the immune system , allowingpreexisting T cells to attack cancer cells. We have used another noncustomizedapproach called in situ vaccination. Immunoenhancing agents are injectedlocally into one site of tumor, thereby triggering a T cell immune responselocally that then attacks cancer throughout the body. We have used a screeningstrategy in which the same syngeneic tumor is implanted at two separate sitesin the body. One tumor is then injected with the test agents, and the resultingimmune response is detected by the regression of the distant, untreated tumor.Using this assay, the combination of unmethylated CG– enrichedoligodeoxynucleotide (CpG)—a Toll-like receptor 9 (TLR9​​) ligand—and anti-OX40antibody provided the most imp ressive results. TLRs are components of theinnate immune system that recognize molecular patterns on pathogens. Low dosesof CpG injected into a tumor induce the expression of OX40 on CD4+ Tcells in the microenvironment in mouse or human tumors. An agonistic anti-OX40antibody can then trigger a T cell immune response, which is specific to theantigens of the injected tumor. Remarkably, this combination of a TLR ligandand an anti-OX40 antibody can cure multiple types of cancer and preventspontaneous genetically driven cancers.

五

【論文標題】AutologousiPSC-Based Vaccines Elicit Anti-tumor Responses In Vivo

【論文作者】RonaldLevy, Mark M. Davis, et al.

【發表時間】2018年1月16日

【發表期刊】CellStem Cell

【論文鏈接】

http://cdn.cnn.com/cnn/2018/images/02/14/cancer.vaccine.study.mice..pdf

【論文編號】doi.org/10.1016/j.stem.2018.01.016

【論文摘要】Cancercells and embryonic tissues share a number of cellular and molecularproperties, suggesting that induced pluripotent stem cells (iPSCs) may beharnessed to elicit anti-tumor responses in cancer vaccines. RNA sequencingrevealed that human and murine iPSCs express tumor-associated antigens, and weshow here a proof of principle for using irradiated iPSCs in autologous anti-tumorvaccines. In a prophylactic setting, iPSC vaccines prevent tumor growth insyngeneic murine breast cancer, mesothelioma, and melanoma models. As anadjuvant, the iPSC vaccine inhibited melanoma recurrence at the resection siteand reduced metastatic tumor load, which was associated with fewer Th17 cellsand increased CD11b+ GR1hi myeloid cells. Adoptivetransfer of T cells isolated from vaccinetreated tumor-bearing mice inhibitedtumor growth in unvaccinated recipients, indicating that the iPSC vaccine promotesan antigen-specific anti-tumor T cell response. Our data suggest ageneralizable strategy f or multiple types of cancer that could prove highlyvaluable in clinical immunotherapy.