Patient Selection and Monitoring for Immunotherapies: Challenges for Immune Checkpoint Antibody and Cell Therapies

2015 ◽  
pp. 85-101
Author(s):  
Noura Choudhury
Keyword(s):  
Patient Selection ◽  
Immune Checkpoint ◽  
Cell Therapies

scholarly journals Immunoexpression of PD-L1 and PD-1 and Its Clinicopathological Correlation in Urothelial Carcinomas

2021 ◽  
Author(s):  
Utpal Kumar ◽  
Michael Leonard Anthony ◽  
Rishabh Sahai ◽  
Ankur Mittal ◽  
Prashant Durgapal ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Patient Selection ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Tumor Resection ◽  
Treatment Protocol ◽  
High Expression ◽  
Urothelial Carcinomas ◽  
Multiple Drugs ◽  
Age And Sex

Abstract Introduction Urothelial carcinomas are the most common types of bladder tumors that have recently shown a changing trend in treatment protocols with the introduction and approval of immune checkpoint inhibitors. The most important immune checkpoint lies with the PD-1–PD-L1 axis. Although multiple drugs have been approved, there is uncertainty about patient selection criteria and diagnostic assays. Recent studies related to the laboratory-developed tests have opened up the horizon of PD-1 and PD-L1 immunohistochemistry even at resource-constrained laboratories. We propose to study these immunohistochemistry markers in our laboratory using newer clones. Materials and Methods We selected 116 consecutive cases of transurethral bladder tumor resection from our laboratory archive and applied PD-1 and PD-L1 immunohistochemistry. The study was approved by the institution's ethics committee. Results We found high expression of PD-1 and PD-L1 in urothelial carcinoma even with different cut-offs of PD-L1. Muscle invasion, lamina invasion, and grade of carcinoma had a statistically significant effect on the expression; however, age and sex did not affect the expression. Conclusion Based on our current study, we can conclude that the clones used in our study show high expression in urothelial carcinoma and can aid in patient selection and treatment protocol, irrespective of age and sex.

scholarly journals Current Immunotherapeutic Approaches in T Cell Non-Hodgkin Lymphomas

Cancers ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 339 ◽  
Author(s):  
Teresa Poggio ◽  
Justus Duyster ◽  
Anna Illert
Keyword(s):  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
T Cell ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Tumor Antigens ◽  
Checkpoint Inhibitors ◽  
Cell Physiology ◽  
Cell Therapies ◽  
Car T

T cell non-Hodgkin lymphoma (T-NHL) is a rare and heterogeneous group of neoplasms of the lymphoid system. With the exception of a few relatively indolent entities, T-NHL is typically aggressive, treatment resistant, and associated with poor prognosis. Relatively few options with proven clinical benefit are available for patients with relapsed or refractory disease. Immunotherapy has emerged as a promising treatment for the management of patients with hematological malignancies. The identification of tumor antigens has provided a large number of potential targets. Therefore, several monoclonal antibodies (alemtuzumab, SGN-30, brentuximab vedotin, and mogamulizumab), directed against tumor antigens, have been investigated in different subtypes of T-NHL. In addition to targeting antigens involved in cancer cell physiology, antibodies can stimulate immune effector functions or counteract immunosuppressive mechanisms. Chimeric antigen receptor (CAR)-T cells directed against CD30 and immune checkpoint inhibitors are currently being investigated in clinical trials. In this review, we summarize the currently available clinical evidence for immunotherapy in T-NHL, focusing on the results of clinical trials using first generation monoclonal antibodies, new immunotherapeutic agents, immune checkpoint inhibitors, and CAR-T cell therapies.

scholarly journals Nanobiotechnology and Immunotherapy: Two Powerful and Cooperative Allies against Cancer

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3765
Author(s):  
Francesco Mainini ◽  
Francesca De Santis ◽  
Giovanni Fucà ◽  
Massimo Di Nicola ◽  
Licia Rivoltini ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Adverse Effects ◽  
Immune Responses ◽  
Immune Checkpoint ◽  
Therapy Resistance ◽  
Immune Checkpoint Blockade ◽  
Cancer Therapies ◽  
Great Efficacy ◽  
Innovative Strategy ◽  
Cell Therapies

A number of novel cancer therapies have recently emerged that have rapidly moved from the bench to the clinic. Onco-immunotherapies, such as immune checkpoint blockade inhibitors and adoptive cell therapies, have revolutionized the field, since they provide a way to induce strong anti-tumor immune responses, which are able to fight cancer effectively. However, despite showing great efficacy in hematological and some solid tumors, unresponsiveness, development of therapy resistance and the development of serious adverse effects, limit their capacity to impact the vast majority of tumors. Nanoparticle-based delivery systems are versatile vehicles for a wide variety of molecular cargoes and provide an innovative strategy to improve conventional onco-immunotherapies. They can be finely tuned to release their contents in the tumor microenvironment, or to deliver combinations of adjuvants and antigens in the case of nanovaccines. In this review, we summarize the recent advancements in the field of nanobiotechnology, to remodel the tumor microenvironment and to enhance immunotherapies.

scholarly journals Poly-IC enhances the effectiveness of cancer immunotherapy by promoting T cell tumor infiltration

2020 ◽  
Vol 8 (2) ◽  
pp. e001224 ◽  
Author(s):  
Hussein Sultan ◽  
Juan Wu ◽  
Valentyna I Fesenkova ◽  
Aaron E Fan ◽  
Diane Addis ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Cell Infiltration ◽  
Mouse Tumor ◽  
Type I ◽  
Antitumor Effects ◽  
Cell Therapies ◽  
T Cell Infiltration

BackgroundImmunotherapies, such as immune checkpoint inhibitors and adoptive cell therapies, have revolutionized cancer treatment and resulted in complete and durable responses in some patients. Unfortunately, most immunotherapy treated patients still fail to respond. Absence of T cell infiltration to the tumor site is one of the major obstacles limiting immunotherapy efficacy against solid tumors. Thus, the development of strategies that enhance T cell infiltration and broaden the antitumor efficacy of immunotherapies is greatly needed.MethodsWe used mouse tumor models, genetically deficient mice and vascular endothelial cells (VECs) to study the requirements for T cell infiltration into tumors.ResultsA specific formulation of poly-IC, containing poly-lysine and carboxymethylcellulose (PICLC) facilitated the traffic and infiltration of effector CD8 T cells into the tumors that reduced tumor growth. Surprisingly, intratumoral injection of PICLC was significantly less effective in inducing tumor T cell infiltration and controlling growth of tumors as compared with systemic (intravenous or intramuscular) administration. Systemically administered PICLC, but not poly-IC stimulated tumor VECs via the double-stranded RNA cytoplasmic sensor MDA5, resulting in enhanced adhesion molecule expression and the production of type I interferon (IFN-I) and T cell recruiting chemokines. Expression of IFNαβ receptor in VECs was necessary to obtain the antitumor effects by PICLC and IFN-I was found to directly stimulate the secretion of T cell recruiting chemokines by VECs indicating that this cytokine-chemokine regulatory axis is crucial for recruiting effector T cells into the tumor parenchyma. Unexpectedly, these effects of PICLC were mostly observed in tumors and not in normal tissues.ConclusionsThese findings have strong implications for the improvement of all types of T cell-based immunotherapies for solid cancers. We predict that systemic administration of PICLC will improve immune checkpoint inhibitor therapy, adoptive cell therapies and therapeutic cancer vaccines.

scholarly journals Targeting HPV in gynaecological cancers – Current status, ongoing challenges and future directions

2020 ◽  
Vol 16 ◽  
pp. 174550652096170
Author(s):  
Shanthini M Crusz ◽  
Karim El-Shakankery ◽  
Rowan E Miller
Keyword(s):  
T Cell ◽  
Human Papilloma Virus ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Human Papilloma Virus Infection ◽  
Current Status ◽  
Curative Intent ◽  
Papilloma Virus ◽  
Cell Therapies ◽  
Cell Immunity

Despite the success of preventive vaccination, the Human Papilloma Virus still accounts for 266,000 deaths annually, as the main causative factor of cervical, vaginal, anal, penile and oropharyngeal cancers. Human Papilloma Virus infects epithelial cells, driving tumourigenesis primarily from incorporation of DNA into the host cellular genome. Translation of two particular Human Papilloma Virus–specific oncoproteins, E6 and E7, are the key drivers of malignancy. If diagnosed early cervical, vaginal and vulval cancers have good prognosis and are treated with curative intent. However, metastatic disease carries a poor prognosis, with first-line systemic treatment providing only modest increase in outcome. Having shown promise in other solid malignancies, immune checkpoint inhibition and therapeutic cancer vaccines have been directed towards Human Papilloma Virus–associated gynaecological cancers, mindful that persistent Human Papilloma Virus infection drives malignancy and is associated with immunosuppression and lack of T-cell immunity. In this review, we discuss novel therapeutic approaches for targeting Human Papilloma Virus–driven gynaecological malignancies including vaccination strategies, use of immunomodulation, immune checkpoint inhibitors and agents targeting Human Papilloma Virus–specific oncoproteins. We also highlight the evolving focus on exciting new treatments including adoptive T-cell therapies.

scholarly journals Invasive Fungal Diseases in Children with Hematological Malignancies Treated with Therapies That Target Cell Surface Antigens: Monoclonal Antibodies, Immune Checkpoint Inhibitors and CAR T-Cell Therapies

2021 ◽  
Vol 7 (3) ◽  
pp. 186
Author(s):  
Ioannis Kyriakidis ◽  
Eleni Vasileiou ◽  
Claudia Rossig ◽  
Emmanuel Roilides ◽  
Andreas H. Groll ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Gemtuzumab Ozogamicin ◽  
Brentuximab Vedotin ◽  
Inotuzumab Ozogamicin ◽  
Cell Therapies ◽  
Invasive Fungal Diseases ◽  
Car T

Since 1985 when the first agent targeting antigens on the surface of lymphocytes was approved (muromonab-CD3), a multitude of such therapies have been used in children with hematologic malignancies. A detailed literature review until January 2021 was conducted regarding pediatric patient populations treated with agents that target CD2 (alefacept), CD3 (bispecific T-cell engager [BiTE] blinatumomab), CD19 (denintuzumab mafodotin, B43, BiTEs blinatumomab and DT2219ARL, the immunotoxin combotox, and chimeric antigen receptor [CAR] T-cell therapies tisagenlecleucel and axicabtagene ciloleucel), CD20 (rituximab and biosimilars, 90Y-ibritumomab tiuxetan, ofatumumab, and obinutuzumab), CD22 (epratuzumab, inotuzumab ozogamicin, moxetumomab pasudotox, BiTE DT2219ARL, and the immunotoxin combotox), CD25 (basiliximab and inolimomab), CD30 (brentuximab vedotin and iratumumab), CD33 (gemtuzumab ozogamicin), CD38 (daratumumab and isatuximab), CD52 (alemtuzumab), CD66b (90Y-labelled BW 250/183), CD248 (ontuxizumab) and immune checkpoint inhibitors against CTLA-4 (CD152; abatacept, ipilimumab and tremelimumab) or with PD-1/PD-L1 blockade (CD279/CD274; atezolizumab, avelumab, camrelizumab, durvalumab, nivolumab and pembrolizumab). The aim of this narrative review is to describe treatment-related invasive fungal diseases (IFDs) of each category of agents. IFDs are very common in patients under blinatumomab, inotuzumab ozogamicin, basiliximab, gemtuzumab ozogamicin, alemtuzumab, and tisagenlecleucel and uncommon in patients treated with moxetumomab pasudotox, brentuximab vedotin, abatacept, ipilimumab, pembrolizumab and avelumab. Although this new era of precision medicine shows promising outcomes of targeted therapies in children with leukemia or lymphoma, the results of this review stress the necessity for ongoing surveillance and suggest the need for antifungal prophylaxis in cases where IFDs are very common complications.

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