Browse
Submit Data
Databases
API
Help

Dataset Information

27 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Development of Immunotherapy Combination Strategies in Cancer.

ABSTRACT: 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.

SUBMITTER: Yap TA

PROVIDER: S-EPMC8178168 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

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 strategies to maximize the benefits of cancer immunotherapy.

Project description: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.

| S-EPMC8475356 | biostudies-literature

Immunotherapy for Triple-Negative Breast Cancer: Combination Strategies to Improve Outcome.

Project description:Due to the absence of hormone receptor (both estrogen receptors and progesterone receptors) along with human epidermal growth factor receptor 2 (HER-2) amplification, the treatment of triple-negative breast cancer (TNBC) cannot benefit from endocrine or anti-HER-2 therapy. For a long time, chemotherapy was the only systemic treatment for TNBC. Due to the lack of effective treatment options, the prognosis for TNBC is extremely poor. The successful application of immune checkpoint inhibitors (ICIs) launched the era of immunotherapy in TNBC. However, the current findings show modest efficacy of programmed cell death- (ligand) 1 (PD-(L)1) inhibitors monotherapy and only a small proportion of patients can benefit from this approach. Based on the basic principles of immunotherapy and the characteristics of the tumor immune microenvironment (TIME) in TNBC, immune combination therapy is expected to further enhance the efficacy and expand the beneficiary population of patients. Given the diversity of drugs that can be combined, it is important to select effective biomarkers to identify the target population. Moreover, the side effects associated with the combination of multiple drugs should also be considered.

| S-EPMC9818757 | 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 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

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

Immunotherapy for glioblastoma: the promise of combination strategies.

Project description:Glioblastoma (GBM) treatment has remained almost unchanged for more than 20 years. The current standard of care involves surgical resection (if possible) followed by concomitant radiotherapy and chemotherapy. In recent years, immunotherapy strategies have revolutionized the treatment of many cancers, increasing the hope for GBM therapy. However, mostly due to the high, multifactorial immunosuppression occurring in the microenvironment, the poor knowledge of the neuroimmune system and the presence of the blood-brain barrier, the efficacy of immunotherapy in GBM is still low. Recently, new strategies for GBM treatments have employed immunotherapy combinations and have provided encouraging results in both preclinical and clinical studies. The lessons learned from clinical trials highlight the importance of tackling different arms of immunity. In this review, we aim to summarize the preclinical evidence regarding combination immunotherapy in terms of immune and survival benefits for GBM management. The outcomes of recent studies assessing the combination of different classes of immunotherapeutic agents (e.g., immune checkpoint blockade and vaccines) will be discussed. Finally, future strategies to ameliorate the efficacy of immunotherapy and facilitate clinical translation will be provided to address the unmet medical needs of GBM.

| S-EPMC8787896 | biostudies-literature

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

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