Browse
Submit Data
Databases
API
Help

Dataset Information

19 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Combination strategies to maximize the benefits of cancer immunotherapy.

ABSTRACT: Immunotherapies such as immune checkpoint blockade (ICB) and adoptive cell therapy (ACT) have revolutionized cancer treatment, especially in patients whose disease was otherwise considered incurable. However, primary and secondary resistance to single agent immunotherapy often results in treatment failure, and only a minority of patients experience long-term benefits. This review article will discuss the relationship between cancer immune response and mechanisms of resistance to immunotherapy. It will also provide a comprehensive review on the latest clinical status of combination therapies (e.g., immunotherapy with chemotherapy, radiation therapy and targeted therapy), and discuss combination therapies approved by the US Food and Drug Administration. It will provide an overview of therapies targeting cytokines and other soluble immunoregulatory factors, ACT, virotherapy, innate immune modifiers and cancer vaccines, as well as combination therapies that exploit alternative immune targets and other therapeutic modalities. Finally, this review will include the stimulating insights from the 2020 China Immuno-Oncology Workshop co-organized by the Chinese American Hematologist and Oncologist Network (CAHON), the China National Medical Product Administration (NMPA) and Tsinghua University School of Medicine.

SUBMITTER: Zhu S

PROVIDER: S-EPMC8475356 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Development of Immunotherapy Combination Strategies in Cancer.

Project description:Harnessing the immune system to treat cancer through inhibitors of CTLA4 and PD-L1 has revolutionized the landscape of cancer. Rational combination strategies aim to enhance the antitumor effects of immunotherapies, but require a deep understanding of the mechanistic underpinnings of the immune system and robust preclinical and clinical drug development strategies. We review the current approved immunotherapy combinations, before discussing promising combinatorial approaches in clinical trials and detailing innovative preclinical model systems being used to develop rational combinations. We also discuss the promise of high-order immunotherapy combinations, as well as novel biomarker and combinatorial trial strategies. SIGNIFICANCE: Although immune-checkpoint inhibitors are approved as dual checkpoint strategies, and in combination with cytotoxic chemotherapy and angiogenesis inhibitors for multiple cancers, patient benefit remains limited. Innovative approaches are required to guide the development of novel immunotherapy combinations, ranging from improvements in preclinical tumor model systems to biomarker-driven trial strategies.

| S-EPMC8178168 | biostudies-literature

Emerging strategies for combination checkpoint modulators in cancer immunotherapy.

Project description:Current immune checkpoint-modulating agents have demonstrated clinical efficacy in certain tumor types, particularly those with a high burden of tumor-specific neoantigens, high tumor-mutational burden, and abundant tumor-infiltrating T cells. However, these tumors often stop responding, with signs of T cells exhaustion, decreased T cell effector function, and upregulated inhibitory checkpoints. To enhance antitumor immunity and rescue exhausted T cells, newer inhibitory and stimulatory checkpoint modulators are being tested as monotherapy or in combination with approved checkpoint inhibitors. In contrast, tumors with low tumor-mutational burden, low neoantigen burden, and a paucity of T cells are immunologically "cold," and therefore first require the addition of agents to facilitate the induction of T cells into tumors. Cold tumors also often recruit immunosuppressive cell subsets, including regulatory T cells, myeloid-derived suppressor cells, and macrophages, and secrete immunosuppressive soluble cytokines, chemokines, and metabolites. To unleash an optimal antitumor immune response, combinatorial therapeutics that combine immune checkpoints with other modalities, such as vaccines, are being developed. From current preclinical data, it appears that combinatorial strategies will provide robust and durable responses in patients with immunologically cold cancers.

| S-EPMC6063475 | biostudies-literature

Combination Strategies of Checkpoint Immunotherapy in Metastatic Breast Cancer.

Project description:Checkpoint immunotherapy is emerging as a new therapeutic approach for metastatic breast cancer. Monotherapy of immunoagents against PD1/PD-L1 or CTLA-4 has shown little efficacy in these patients. Recently, to determine the optimal use of immunotherapy, there has been a rapid expansion in the number of clinical trials developing immunotherapy combinations. These combination therapeutic approaches can enhance various aspects of cancer immunity, such as tumor antigenicity or intratumor T cell infiltration, which provides a theoretical basis for combining them with checkpoint immunotherapy to achieve synergistic effects. Here, we review the available data and ongoing efforts to establish the safety and efficacy of immunoagents in combination with chemotherapy, radiotherapy, HER2-targeted therapy, CDK4/6 inhibitors, PARP inhibitors, and another checkpoint immunoagents.

| S-EPMC7133118 | biostudies-literature

Combination Immune Checkpoint Blockade Strategies to Maximize Immune Response in Gynecological Cancers.

Project description:PURPOSE OF REVIEW:Immune checkpoint blockade targeting PD-1 and PD-L1 improves immune recognition of tumor cells but had only modest success in gynecological cancers as monotherapy. Growing focus has been placed on combination immunotherapy strategies to overcome this resistance, and this review serves to discuss some of the most promising studies in gynecological cancers. RECENT FINDINGS:PD-1- and PD-L1-targeting antibodies are being combined with many novel agents including anti-CTLA-4 antibodies, PARP inhibitors, targeted agents, and traditional chemotherapy in promising studies with the hopes of increasing the immune response and overcoming resistance by targeting other pathways. Novel immune techniques including vaccines and adoptive cell therapies are also being implemented in gynecological cancers. Immune checkpoint combinations and novel immunotherapy strategies have demonstrated potential to overcome resistance to PD-1/PD-L1 blockade in gynecological cancers. Identification of biomarkers of response and resistance is a priority to tailor specific combination therapies to the appropriate patients.

| S-EPMC6244932 | biostudies-literature

Immunotherapy combination strategies (non-chemotherapy) in non-small cell lung cancer.

Project description:Immune checkpoint inhibitors enhance the activation and antitumor activity of the immune system, resulting in durable response rates in a select group of patients. Cytotoxic T lymphocyte antigen 4 (CTLA4) inhibitors target the inhibitory interaction between CTLA4 and CD80 or CD86. Programmed death 1 (PD1) inhibitors target the interaction between PD1 receptors on T-cells and PD-ligand 1 (PD-L1) and PD-ligand 2, blocking the inhibitory signaling and resulting in activation of T-cell effector function. These therapeutic drugs were originally evaluated in patients with metastatic melanoma before expansion to all tumor types, including non-small cell lung cancer (NSCLC) with promising results. The PD1 inhibitors such as pembrolizumab have now received FDA approval in the first-line setting for patients with positive PD-L1 expression tumor types; however, only a portion of patients have shown objective and sustainable responses. To expand the number of patients with observed response to immunotherapeutic agents including patients with negative PD-L1 expression tumors, clinical trials are ongoing to assess the safety and efficacy of combination immune checkpoint inhibitors and combination immune checkpoint inhibitors with targeted therapy. Immune checkpoint inhibitors have been found to be a promising therapeutic drug class with sustainable response rates and a tolerable safety profile, and efforts continue to improve these drugs in patients with NSCLC.

| S-EPMC5861267 | biostudies-literature

Combination strategies of immunotherapy in non-small cell lung cancer: facts and challenges.

Project description:AbstractImmunotherapy has dramatically altered the treatment of non-small cell lung cancer. Currently, the emergence of combination strategies in immunotherapy has brightened the prospects of improved clinical outcomes and manageable safety profiles in the first/second-line settings. However, sub-optimal response rates are still observed in several clinical trials. Hence, alternative combination models and candidate selection strategies need to be explored. Herein, we have critically reviewed and commented on the published data from several clinical trials, including combined immunotherapy and chemotherapy, anti-angiogenic agents, epidermal growth factor receptor/anaplastic lymphoma kinase tyrosine kinase inhibitors, radiotherapy, and other immune checkpoint inhibitors.

| S-EPMC8382384 | biostudies-literature

Combination immunotherapy and radiation therapy strategies for pancreatic cancer-targeting multiple steps in the cancer immunity cycle.

Project description:Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease, with its mortality rate approaching its incidence rate every year. Accordingly, much interest has been generated in harnessing the immune system in order to improve survival outcomes for these patients. Pancreatic cancer is not thought to be as immunogenic as other cancers that have seen promising results with immune checkpoint inhibitors alone, therefore likely several targets within the cancer-immunity cycle will need to be employed for successful treatment. We sought to investigate both the current state of the field in immunotherapy in PDAC with a special emphasis on combined approaches with radiation therapy (RT). We also summarized ongoing clinical trials that are examining the use of radiotherapy with other immune-stimulating agents in the treatment of PDAC. A PubMed and clinicaltrials.gov search was conducted using the following search terms, either alone or in combination: "pancreatic cancer", "immunotherapy", and "abscopal effect". Open clinical trials were reviewed and included if they involved both RT and other immune-stimulating agents. Pancreatic cancers tend to reside within immune-suppressive tumor microenvironments (TME), express PD-L1, and secrete several immuno-suppressive agents, such as TGF-B, IL-10, indoleamine 2,3-dioxygenase, galectin-1. Whole-cell vaccine therapies, peptide and protein vaccines, dendritic cell vaccines, and vaccines with micro-organisms have been investigated by themselves with promising results. Open clinical trials are currently investigating the use of these vaccines, which increase antigen presentation, with treatments that stimulate release of tumor antigens including RT. There are currently at least 21 open clinical trials investigating the combination of RT with other immune-stimulating agents. The combination of RT and immunotherapy may be a promising avenue for PDAC treatment and deserves further research.

| S-EPMC6286952 | biostudies-other

Metastatic castration-resistant prostate cancer: new therapies, novel combination strategies and implications for immunotherapy.

Project description:For the past decade, docetaxel has remained the global standard of care for frontline treatment of metastatic castration-resistant prostate cancer (mCRPC). Until recently, there were limited options for patients with mCRPC following docetaxel failure or resistance, but now the approved treatment choices for these patients have expanded to include abiraterone acetate, cabazitaxel and enzalutamide. Additionally, the radioactive therapeutic agent radium-223 dichloride has been recently approved in patients with CRPC with bone metastases. Although each of these agents has been shown to convey significant survival benefit as a monotherapy, preclinical findings suggest that combining such innovative strategies with traditional treatments may achieve additive or synergistic effects, further augmenting patient benefit. This review will discuss the transformation of the post-docetaxel space in mCRPC, highlighting the spectrum of newly approved agents in this setting in the USA and the European Union, as well as summarizing treatments with non-chemotherapeutic mechanisms of action that have demonstrated promising results in recent phase 3 trials. Lastly, this review will address the potential of combinatorial regimens in mCRPC, including the pairing of novel immunotherapeutic approaches with chemotherapy, radiotherapy or androgen ablation.

| S-EPMC4876694 | biostudies-literature

Stereotactic Radiotherapy for Hepatocellular Carcinoma, Radiosensitization Strategies and Radiation-Immunotherapy Combination.

Project description:Stereotactic body radiotherapy (SBRT) is an emerging ablative modality for hepatocellular carcinoma (HCC). Most patients with HCC have advanced disease at the time of diagnosis, and therefore, are not candidates for definitive-intent therapies such as resection or transplantation. For this reason, various alternative local and regional therapies have been used to prevent disease progression, palliate symptoms, and delay liver failure. Stereotactic body radiation therapy is a non-invasive technique of delivering ablative doses of radiation to tumors while sparing normal or non-tumor hepatic tissue. Incorporation of SBRT in multidisciplinary HCC management is gradual, initially applied when other liver-directed therapies have failed or are contraindicated, and tried in combination with other locoregional or systemic therapies for more unfavorable conditions by more experienced teams. In order to improve SBRT therapeutic ratio, there has been much interest in augmenting the effect of radiation on tumors by combining it with chemotherapy, molecularly targeted therapeutics, nanoparticles, and immunotherapy. This review aims to synthesize available evidence to evaluate the clinical feasibility and efficacy of SBRT for HCC, and to explore novel radio-potentiation concepts by combining SBRT with novel therapeutics. It is expected that those approaches would result in improved therapeutic outcomes, even though many questions remain with regard to the optimal way to assemble treatments. Further trials are needed to evaluate and consolidate these promising therapies for HCC.

| S-EPMC7825787 | biostudies-literature

Cancer immunotherapy: Strategies for personalization and combinatorial approaches.

Project description:The results of recent clinical trials using novel immunotherapy strategies such as immune checkpoint blockade and adoptive T-cell therapy approaches including CAR T-cell therapy have clearly established immunotherapy as an important modality for the treatment of cancer besides the traditional approaches of surgery, radiotherapy, and chemotherapy or targeted therapy. However, to date immunotherapy has been shown to induce durable clinical benefit in only a fraction of the patients. The use of combination strategies is likely to increase the number of patients that might benefit from immunotherapy. Indeed, over the last decade, the characterization of multiple immune resistance mechanisms used by the tumor to evade the immune system and the development of agents that target those mechanisms has generated a lot of enthusiasm for cancer immunotherapy. But a critical issue is to determine how best to combine such agents. This review will focus on novel immunotherapy agents currently in development and discuss strategies to develop and personalize combination cancer immunotherapy strategies.

| S-EPMC4684975 | biostudies-other

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data