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Biology And Methodology Of Whole-Body Hyperthermia
Published in Leopold J. Anghileri, Jacques Robert, Hyperthermia in Cancer Treatment, 2019
H. Ian Robins, Alan J. Neville
Historically, circulatory, immune, and inflammatory responses have long been implicated in the host defenses against both primary tumors and metastatic disease. Pyrexia became recognized as a possible additional factor at the end of the last century, when, following empiric observations of tumor regressions, in febrile cancer patients fevers were deliberately induced by the injection of bacterial filtrates (Coley’s toxins).25,26 It was recognized that in addition to reported responses, some patients developed tachyphylaxis to the induction of fever by the toxins, suggesting that the heat killing of human cancer involved recruitment of immunological or inflammatory mediators.26 More recently, the concept of hyperthermic stimulation of the immune system by heat-damaged cancer cells acting as antigens was proposed by Strauss et al.,114 Strauss,115 and Stehlin et al.116 Consistent with this, Mondovi et al.117 demonstrated increased antigenicity of Ehrlich ascites cells after heat treatment and Pantazatos et al.118 showed hyperthermic sensitization of a human colon cancer cell line to lysis by antibodies and complement. Other workers, however, using the same or similar systems have reported contradictory results.119,120 Whatever the truth of the argument, it is apparent that “local” heating or irradiation of animal or human tumors may lead to tumor regression at distant anatomic sites,115,116,121,122 the so-called “abscopal” response, which implies a systemic, possibly immune response.
Therapy with Oncolytic Clostridium novyi-NT: From Mice to Men
Published in Ananda M. Chakrabarty, Arsénio M. Fialho, Microbial Infections and Cancer Therapy, 2019
Another approach capitalizes on the ability of certain bacterial species to colonize and proliferate in tumors with necrosis or hypoxia, conditions not found in healthy metabolically active tissues. Using bacteria to fight cancer is not a modern concept. The history goes back to the late 1800s, when Dr. William B. Coley, a surgeon at the then New York Cancer Hospital, inoculated his patients in a systematic way with cultures of the erysipelas-causing streptococcal bacteria [19, 20]. Coley hypothesized that the bacterial infection would elicit a robust anticancer immune response. This practice has earned him the reputation as a pioneer in cancer immunotherapy. The initial streptococcal inoculation and subsequent use of the famous Coley’s toxins, a mixture consisting of heat-inactivated Streptococci and Serratia marcescens, generated mixed results with sporadic success and significant toxicity. The idea revived years later when a better understanding about the tumor microenvironment was achieved and recombinant DNA technology became available to generate more potent and less toxic bacterial strains by genetic engineering. Many bacterial strains (mostly anaerobic) have since shown preferential targeting of solid tumors [21–28]. Among the most investigated are various strains of Salmonella, Clostridium, and Listeria, some of which have been tested in clinical trials [27, 29–33]. The clinical development of live bacteria as therapeutic agents for cancer has been challenging because of potential severe toxicities associated with infection from live bacteria. One remarkable clinical success is the use of bacillus Calmette–Guérin (BCG) in the treatment of bladder cancer [34]. BCG is an attenuated live strain of Mycobacterium bovis originally generated as a vaccine for tuberculosis. BCG therapy by intravesical administration was first documented in the 1970s and has since become an important treatment option for transitional-cell carcinoma in situ of the bladder [35–37]. It is believed that BCG’s therapeutic effect is mainly due to its immunomodulatory activity [38–40].
Unblinding the watchmaker: cancer treatment and drug design in the face of evolutionary pressure
Published in Expert Opinion on Drug Discovery, 2022
Sophia Konig, Hannah Strobel, Michael Grunert, Marcin Lyszkiewicz, Oliver Brühl, Georg Karpel-Massler, Natalia Ziętara, Katia La Ferla-Brühl, Markus D. Siegelin, Klaus-Michael Debatin, Mike-Andrew Westhoff
Immunotherapy has come a long way from the use of Coley’s Toxins in 1893 to the Nobel Prizes awarded to James Allison and Tasuku Honjo in 2018 [138]. In the last fifteen years several immunotherapeuticals have demonstrated their clinical potential, such as CAR-T cells, the cancer vaccine sipuleucel-T or ipilimumab and nivolumab [138]. However, while those successes have been predominantly shown with malignancies that can be treated directly, such as melanoma, lymphoma, and leukemia, several challenges remain, in tumor types which are immunological cold, as well as in individual cases where the malignancy is generally considered immunologically hot [139]. Interestingly, there are several cancers which have a low mutational burden (Figure 1) and which therefore only present a limited variation of neoepitopes [140]. While even low mutational load should suffice to produce neoepitopes [141], there is also evidence that responsiveness to immunotherapy is associated with certain genetic alterations, such as enrichment of PTEN mutations in non-responders and enrichment of MAPK pathway alterations in responders [142]. In essentially incurable tumors, where conventional therapy has been shown to potentially synergize with immunotherapy, such as glioblastoma [143], one could therefore imagine a high-risk strategy increasing the genetic instability and/or mutational load of the tumor to make it promising target of immunotherapy. However, activation of the immune system leads to an additional complexity in landscape steering, as the immune system also relies on evolutionary selection and stochastic events.
Could COVID-19 induce remission of acute leukemia?
Published in Hematology, 2021
Eman Z. Kandeel, Lobna Refaat, Raafat Abdel-Fatah, Mohamed Samra, Ahmed Bayoumi, Mona S. Abdellateif, Hend Abdel-Hady, Mohamed Ali, Medhat Khafagy
Our results of the two presented cases are in line with Challenor and Tucker case presentation, who also observed a remission condition in a Hodgkin Lymphoma patient. They reported that the lymphadenopathy subsided after COVID infection [6]. This condition may be explained that the COVID-19 infection could potentially evoke an anti-tumor immune response through cross-reactivity of the virus-specific T cells with tumor antigens, or through non-specific activation of the natural killer cells by the inflammatory cytokines produced in response to viral infection [6]. Similarly, Buckner et al. reported a spontaneous regression in a patient with diffuse large B-cell lymphoma co-existed with pneumonia and Clostridium difficile colitis. They proposed that this regression might be due to stimulation of the immune system with the co-existing pathogen [7]. This leads to cross-reactivity of pathogen-specific T cells with tumor antigens, similar to the alloreactivity induced by viral-specific CD8 T cells that bind to human leukocyte antigen molecules [8,9]. These responses were used many times in the past in a trial performed by Starnes, for curing specific types of cancers like late-stage sarcoma using streptococcal infection, which was the base of Coley’s toxins theory [10]. Another explanation could be that COVID-19 may act as an oncolytic virus, which is causing destruction of the tumor cells and release of the tumor-associated antigen (TAAs) from the tumor cells. These TAAs stimulate the immune system of the host against leukemia cells with cytotoxicity and apoptosis causing regression of the disease [11].
Research progress and clinical application of predictive biomarker for immune checkpoint inhibitors
Published in Expert Review of Molecular Diagnostics, 2019
Ke Ma, Qingqing Jin, Miao Wang, Xin Li, Yuyang Zhang
At the end of the nineteenth century, Coley reported that injecting Coley’s toxins into malignant tumors, induced tumor regression, which pioneered the immunotherapy of malignant tumors. Today, immunotherapy based on checkpoint inhibitors has brought cancer treatment into an exciting era. However, this new treatment mode also brings many new problems to the clinic, such as predicting the efficacy of immunotherapy and its adverse reactions. Complexity and dynamic changes of the human immune system pose great challenges for the development of immunotherapy markers. Although several markers have been identified, none have achieved satisfactory results. New detection techniques, accurate molecular typing, and close and complete immune surveillance will bring new hope for finding predictive markers of immunotherapy and combined immunotherapy.