PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Cancer immunotherapy”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed2025

ImmunoTar-integrative prioritization of cell surface targets for cancer immunotherapy.

MOTIVATION: Cancer remains a leading cause of mortality globally. Recent improvements in survival have been facilitated by the development of targeted and less toxic immunotherapies, such as chimeric antigen receptor (CAR)-T cells and antibody-drug conjugates (ADCs). These therapies, effective in treating both pediatric and adult patients with solid and hematological malignancies, rely on the identification of cancer-specific surface protein targets. While technologies like RNA sequencing and proteomics exist to survey these targets, identifying optimal targets for immunotherapies remains a challenge in the field. RESULTS: To address this challenge, we developed ImmunoTar, a novel computational tool designed to systematically prioritize candidate immunotherapeutic targets. ImmunoTar integrates user-provided RNA-sequencing or proteomics data with quantitative features from multiple public databases, selected based on predefined criteria, to generate a score representing the gene's suitability as an immunotherapeutic target. We validated ImmunoTar using three distinct cancer datasets, demonstrating its effectiveness in identifying both known and novel targets across various cancer phenotypes. By compiling diverse data into a unified platform, ImmunoTar enables comprehensive evaluation of surface proteins, streamlining target identification and empowering researchers to efficiently allocate resources, thereby accelerating the development of effective cancer immunotherapies. AVAILABILITY AND IMPLEMENTATION: Code and data to run and test ImmunoTar are available at https://github.com/sacanlab/immunotar.

Humans↗
PubMed2017

Addressing current challenges in cancer immunotherapy with mathematical and computational modelling.

The goal of cancer immunotherapy is to boost a patient's immune response to a tumour. Yet, the design of an effective immunotherapy is complicated by various factors, including a potentially immunosuppressive tumour microenvironment, immune-modulating effects of conventional treatments and therapy-related toxicities. These complexities can be incorporated into mathematical and computational models of cancer immunotherapy that can then be used to aid in rational therapy design. In this review, we survey modelling approaches under the umbrella of the major challenges facing immunotherapy development, which encompass tumour classification, optimal treatment scheduling and combination therapy design. Although overlapping, each challenge has presented unique opportunities for modellers to make contributions using analytical and numerical analysis of model outcomes, as well as optimization algorithms. We discuss several examples of models that have grown in complexity as more biological information has become available, showcasing how model development is a dynamic process interlinked with the rapid advances in tumour-immune biology. We conclude the review with recommendations for modellers both with respect to methodology and biological direction that might help keep modellers at the forefront of cancer immunotherapy development.

Computer Simulation↗
PubMed1979

Cancer immunotherapy.

Important contributions that stimulated studies in cancer immunotherapy included: (1) the discovery of tumour-associated antigens; (2) the observation that infection with bacille Calmette-Guérin (BCG) in animals was protective against tumour challenge; and (3) the observation that immunodepression due either to malignant disease or to treatment of the disease, was, in some instances, related to prognosis. Immunotherapy trials with microbial agents have involved attempts to obtain a local effect by injecting the agent into the tumour or into the region of the tumour and to obtain a "systemic" effect distant from the site of injection. Trials with active specific immunotherapy involving tumour cells or tumour cell extracts have frequently involved the combination of these specific agents with a nonspecific adjuvant such as BCG. Recent studies with thymosin and levamisole in patients with lung cancer and other types of malignant disease have shown prolonged survival in the groups receiving immunotherapy.

Animals↗
PubMed1977

[Immunotherapy of warts. Is it an experimental model for cancer immunotherapy?].

The warts produced by virus Papova, provedly cancerous, have immunological characteristics that allow to establish some analogies with cancer. Its immunotherapy is studied with levamisole and by means of a delayed immunity reaction "in situ" with regulated intensity. The level of delayed immunity in the patient with warts is established by quantitative DNCB test, finding that the same is impaired in 60% of men and 87% of women. The levamisol therapy cures 54% of warts. The patients that not cure but improve their delayed immunity level after the treatment with levamisol, are submitted to external application of DNCB, using a concentration calculated on the quantitative test results. With regard to their delayed immunity we introduce a new group of patients: the hiperergic type or reactive to 2,5 microgram of DNCB that cures their warts by the sole action of the test. Once obtained the curve of the distribution of delayed immunity values in the warts population before and after the levamisole therapy, we observe that the first is identical to that of cancer patients. In view of the tight relation among diseases with impaired delayed immunity, such as warts, herpes, aphtas, piodermitis and cancer (residual or postsurgical), we propose the same management, control and immunotherapy for all of them.

Clinical Trials as Topic↗
PubMed2026

Cancer Immunotherapy: Therapeutic Limitations and Next-Generation Precision Strategies.

Cancer immunotherapy has reshaped oncology, largely through immune checkpoint inhibitors that release the brakes on tumor-reactive T cells. Yet the benefit remains uneven, and that unevenness traces back to a few basic biological limits. Checkpoint blockade amplifies immunity that is already present; it does not create tumor specificity de novo. Poor Ag quality, defective Ag presentation, a suppressive microenvironment, and epigenetically fixed T-cell exhaustion together set a ceiling on what checkpoint release can achieve. Next-generation strategies try to move past these limits by reorganizing immunotherapy around the functional layers of the immune response. Cancer vaccines define tumor-specific neoantigens and expand the responses against them. Ab-based approaches tune inhibitory signaling, draw immune cells toward the tumor, and trigger immunogenic cell death. Cellular therapies-chimeric Ag receptor T cell, TCR-engineered T cells, and tumor-infiltrating lymphocytes (TILs)-boost effector potency, with TIL therapy notable for preserving tumor-reactive repertoires shaped in vivo. Rather than rivals, these modalities are best seen as complementary layers-Ag definition, immune priming, effector optimization, and microenvironmental conditioning-to be combined in a programmable way. As genomic profiling, immunopeptidomics, and high-dimensional immune monitoring mature, the field is shifting from checkpoint-centered release toward precision immunoengineering, in which tumor-specific immunity is deliberately designed, aligned, and sustained.

Cancer vaccines↗
PubMed1978

Cancer immunotherapy.

This paper briefly reviews some mechanisms of tumor immunity and the principles of cancer immunotherapy. Cellular and humoral immunity can both influence tumor cells. Most of the cells belonging to the immune system can act on neoplastic cells. T cells can kill them, macrophages inhibit their growth, and K cells through their Fc receptor also destroy antibody-coated tumor cells. Cancer patients have usually depressed cellular immune functions. The goal of immunotherapy is to amplify the immune reactions in order to destroy the tumor cells. The modalities of immunotherapy are described. They may become important as adjuvant therapy. Immunotherapy has already been successfully in skin cancers, lung cancer and acute myeloblastic leukemia.

Humans↗
PubMed1975

Effect of intravenous B.C.G. in guineapigs and pertinence to cancer immunotherapy in man.

Intravenous injection of heat-killed or irradiated B.C.G into tuberculin-positive guineapigs produced macroscopic lesions in the lung when examined 10 days or 4 or 6 weeks later. Microscopically, granulomas typical of a delayed hypersensitivity reaction were seen. Intravenous B.C.G. in normal guineapigs did not produce lesions. At equivalent doses to the killed vaccine, viable vaccine caused only mild lesions. Liver lesions were also found on early examination but by 4 weeks had almost resolved. Acid/alcohol-fast bacteria were only rarely detected. Purified portein derivative did not produce lesions, and antihistamine treatment did not modify the results. These results suggest that B.C.G. should be given by the intravenous route for cancer immunotherapy in man with great caution, especially in tuberculin-sensitive persons. The guineapig observations stress that hypersensitisation is a potential complicating feature of cancer immunotherapy, and this is discussed in the light of published clinical experience of B.C.G. by various routes. It is concluded that B.C.G. vaccines with a high proportion of viable organisms are to be preferred.

Animals↗
PubMed1977

Cancer immunotherapy with surgery.

With the recent advances in the immunological surveillance system, an understanding of the role of host immunity has become essential to the management of carcinogenesis, tumor proliferation, recurrence and metastasis. Although it is important to continue chemical and surgical treatment of cancer, support of the anti-tumor immune system of the host should also be considered. Long term remission has been reported in leukemia by treating with BCG after chemotherapy whereas surgical treatment is usually more effective in preventing cancer recurrence in digestive organ cancer. The first step is extirpating the tumor as thoroughly as possible and the second step is chemo-immunotherapy. Cancer immunity, however weak, constitutes the basis for other treatments in selectively attacking cancer cells remaining after surgery, chemotherapy or irradiation. Immunotherapy should thus not replace chemotherapy or radiotherapy, but these methods should be employed in combination to attain more favorable results.

Aged↗
PubMed2026

Predictive biomarkers in cancer immunotherapy for genitourinary malignancies.

Immunotherapy has transformed the management of genitourinary cancers, offering durable responses in selected patient groups. However, the clinical benefit of immune checkpoint inhibitors varies significantly across renal cell carcinoma, urothelial carcinoma, and prostate cancer, underscoring the need for reliable predictive biomarkers. This review summarizes current knowledge on established and emerging biomarkers, including PD L1 expression, tumor mutational burden, molecular subtypes, genomic alterations, tumor microenvironment characteristics, circulating biomarkers, microbiome influences, and multi omic integrative approaches. We discuss their potential clinical relevance, limitations, and applicability across different tumor types. Future directions emphasize the development of composite biomarkers, standardization of testing platforms, real time monitoring strategies, and the integration of advanced technologies such as artificial intelligence and spatial profiling. Understanding and validating these biomarkers will be essential for optimizing personalized immunotherapy in genitourinary cancers.

Circulating tumor DNA↗
PubMed2025

Oncogenic roles of young human de novo genes and their potential as neoantigens in cancer immunotherapy.

Young human de novo genes, recently emerging from non-coding regions, are expected to contribute to human-specific traits and diseases. However, systematic explorations of this connection have been lacking. Here, we report 37 recently originated de novo genes in humans, with their evolution and characteristics defined within an updated genomic context. The expression of these genes is significantly upregulated and temporospatially expanded in tumors, partially associated with extrachromosomal DNA amplification. Depletion of 57.1% of these genes suppresses tumor cell proliferation, underscoring their roles in tumorigenesis. As a proof of concept, we developed mRNA vaccines expressing ELFN1-AS1 and TYMSOS-young genes specifically expressed during early development but reactivated exclusively in tumors. In humanized mice, these vaccines triggered specific T cell activation and inhibited tumor growth. The antigens derived from these genes are immunogenic and capable of eliciting antigen-specific T cell activation in colorectal cancer patients. These findings underscore young human de novo genes as neoantigens in cancer immunotherapy.

Humans↗
PubMed2026

Miniature and versatile genome regulation TnpB-ωRNA toolkits facilitate cancer immunotherapy.

CRISPR‒Cas systems represent powerful tools for genome regulation. However, the large size of Cas proteins limits their efficient delivery via an adeno-associated virus (AAV), thereby restricting their clinical translation. Here, we engineer the IS200/IS605 transposon-encoded nuclease TnpB, along with its ωRNA scaffold, to create an enhanced TnpB system, which serves as a compact toolkit for gene activation, genome editing, and base editing. The gene activator enTnpBa increases expression by 2889-fold with a minimized 93 nt ωRNA and robustly activates endogenous genes in mammalian cells. We develop a single-AAV-based regimen for immune activation (AAV-ImmunAct) that delivers enTnpBa to activate CXCL9, IL-15, and IFN-γ. AAV-ImmunAct effectively enhances T cell migration and activation, increases killing of cancer cell lines and patient-derived organoids, and synergizes with anti-PD-1 therapy in humanized mice. Here, we establish enTnpB as a compact and versatile platform for genome regulation and a promising tool for cancer immunotherapy.

Humans↗
PubMed2025

Fluorinated Ionizable Lipids for Efficient Spleen-Targeted mRNA Delivery in Cancer Immunotherapy.

Efficient and selective mRNA delivery to immune-related organs, particularly the spleen, remains a major barrier to the broader clinical translation of mRNA therapeutics. Here, leveraging the clinically approved SM-102/ALC-0315 ionizable lipid scaffold, we rationally designed a combinatorial library of fluorinated ionizable lipids (FILs) by systematically modulating hydrophobic tails and fluorine stoichiometry. Through synthesis and evaluation of 74 candidate FILs, we identify SSC6F5 lipid nanoparticles (LNPs) as a lead formulation with exceptional spleen-targeting specificity (>90%) across intravenous, intramuscular, and subcutaneous administrations. Compared to clinically approved SM102 LNPs and spleen-tropic SM102/18PA (SORT) LNPs, intravenously administered SSC6F5 LNPs achieve 10.6-fold and 63.1-fold higher splenic mRNA transfection, respectively. Proteomic analysis of protein corona on SSC6F5 LNPs reveals significant enrichment of apolipoprotein D (Apod) and reduction in apolipoprotein H (Apoh), implicating a novel endogenous recognition pathway driving enhanced spleen targeting. Functionally, SSC6F5 LNPs enable efficient genome editing in splenic macrophages, dendritic cells, T cells, and B cells in Ai9 mice, and elicit potent CD8+ T cell and humoral responses in a B16-OVA murine melanoma model, resulting in significant tumor growth inhibition. These findings establish fluorinated lipids as a mechanistically distinct and translationally versatile platform for precision spleen-targeted mRNA delivery in gene editing and cancer immunotherapy.

Animals↗
PubMed2026

Predictive Biomarkers for Immune Checkpoint Inhibitor Efficacy: Challenges, Innovations, and a Pathway to Precision Medicine in the Era of Cancer Immunotherapy.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have transformed oncology practice. However, treatment response remains heterogeneous, rendering predictive biomarkers critical for optimal patient care. The 3 established biomarkers, programmed death-ligand 1, tumor mutational burden (TMB), and microsatellite instability-high/deficient mismatch repair, are approved and clinically validated but are modest predictors of benefit. As a result, multiple novel predictive biomarkers remain under investigation. CONTENT: This review highlights established and investigational predictive ICI efficacy biomarkers. For established biomarkers, we describe biology, assay modalities, approved companion diagnostics, landmark studies, and notable limitations. Due to the multisystem nature of antitumor immune effects, investigational biomarkers span multiple domains, including tumor genomic biomarkers (e.g., mutational signatures, TMB, neoantigen clonality), tumor microenvironment (e.g., tumor-infiltrating lymphocytes [TILs], tertiary lymphoid structures), systemic immune biomarkers (e.g., cytokines, autoantibodies, glycoproteins, peripheral blood mononuclear cells), and the microbiome (e.g., gastrointestinal microbial diversity, responder-enriched taxa). SUMMARY: The established biomarkers PD-L1, TMB, and microsatellite instability-high/deficient mismatch repair inform ICI use in clinical practice but have important limitations. Multiple investigational biomarkers show promise in refining patient selection and optimizing therapy. Moving forward, increased assay harmonization, prospective validation, and standardized parameters may improve performance. Composite models integrating complementary signals across domains may further individualize treatment and lead to an era of personalized cancer immunotherapy.

Humans↗
PubMed2026

Engineered Bacteriophages in Cancer Immunotherapy: Emerging Concepts and Potential Integration with CAR-T Cell Therapy.

Due to antigen heterogeneity, restricted immune cell trafficking and an immunosuppressive, nutrient-restricted tumour microenvironment, solid tumours remain resistant to modern immunotherapies. Engineered bacteriophages offer a modular framework to overcome these obstacles: programmable virus-like particles with scalable production. Through genome engineering, capsid decoration with mammalian cell-targeting ligands, or hybrid AAV/phage systems, engineered bacteriophages can display tumour-associated antigens, enhance receptor-mediated uptake and deliver therapeutic payloads such as cytokines, chemokines and suicide genes without naturally infecting mammalian cells. These features support their use as vaccine platforms, immunological adjuvants and targeted gene-delivery vehicles. These may enable more precise, tumour-localized therapeutic intervention. Phages can engage innate immune pathways, including TLR9, TLR3/7/8, cGAS-STING and AIM2, promoting dendritic cell maturation and inflammatory mediators that may convert immunologically "cold" tumours into inflamed microenvironments. Their multivalent antigen display enhances B- and T-cell priming, while cDC1-mediated cross-presentation supports cytotoxic CD8+ T-cell responses and immunological memory. In CAR-T therapy, engineered phages may improve tumour homing through chemokine modulation, support persistence through local cytokine delivery, reduce antigen escape by presenting multiple tumour epitopes, and limit T-cell exhaustion through dominant-negative receptor strategies or local checkpoint blockade. This review summarizes engineering approaches, delivery systems, manufacturing, biodistribution, dosing, and safety issues, including immunogenicity, pre-existing anti-phage antibodies and horizontal gene transfer. It also distinguishes therapeutic engineered phage particles from phage display technologies used for molecular discovery. Despite encouraging results integrating modified bacteriophages with CAR-T cell therapy, the evidence remains mostly preclinical, indicating both substantial translational prospects and crucial obstacles for future clinical development.

CAR-T cell therapy↗
PubMed2025

Rewiring tumor immunity via zinc finger proteins: a new frontier in cancer immunotherapy.

BACKGROUND: Zinc finger proteins (ZFPs) represent the largest and most structurally diverse family of transcription factors in the human genome. They function through characteristic zinc finger domains that enable specific binding to DNA, RNA, and proteins, playing a central regulatory role in the tumor immune microenvironment. MAIN BODY: This review systematically examines the dual functions of ZFPs in dynamically regulating both innate and adaptive immune responses in cancer. At the innate immunity level, ZFPs precisely control dendritic cell (DC) fate determination, dictate macrophage polarization, balance natural killer (NK) cell activation, mediate myeloid-derived suppressor cell (MDSC) immunosuppressive function, and modulate innate immune sensors and inflammasomes. Within adaptive immunity, ZFPs critically influence T cell effector function and regulate B cell differentiation. Building on these, diverse immunotherapeutic strategies targeting ZFPs are now emerging. These include gene-editing, small molecules and proteolysis-targeting chimeras (PROTACs), synergistic combinations with immune checkpoint blockade, and ZFP-engineered chimeric antigen receptor T (CAR-T) cells. CONCLUSIONS: As pivotal nodes within the tumor immune regulatory network, ZFP-targeting strategies offer novel opportunities to overcome current therapeutic bottlenecks.

Humans↗
PubMed1978

Cancer immunotherapy with levamisole.

Levamisole, an agent acting upon depressed cellular immunity, enhancing and normalizing it and consequently showing antitumor activity in the cancer-bearing body, was administered to patients with gastrointestinal cancer at a daily dose of 150 mg for three consecutive days every other week, starting as a rule, three days before operation. The patients were evaluated for survival. Of the 143 patients (66 with curative resection, 40 with noncurative resection and 37 without resection) who received levamisole therapy for one month or more, 57 survived postoperatively six months and of 44 treated 37 survived one year. In this study, 185 patients with gastrointestinal cancer were used for comparison purposes. The six-month survival rate was 100% (23/23) in the levamisole treated group and 95.3% (102/107) in the control group after curative resection (p greater than 0.5), 100% (23/23) and 90.5% (49/54) after noncurative resection (p less than 0.01), and 72.5% (8/11) and 33.3% (9/24), respectively, in non-resectable patients (p less than 0.01). The one-year survival rate was 100% (21/21) and 95.3% (102/107) after curative resection (p greater than 0.5), 77.8% (14/18) and 59.3% (32/54) after noncurative resection (0.05 less than p less than 0.1), and 40% (2/5) and 8.3% (2/24) in non-resectable patients (0.05 less than p than 0.1) in the levamisole group and in the control group, respectively. The difference in survival in survival rates between levamisole-treated and control groups was most prominent in the non-resectable patients followed by those undergoing noncurative resection and curative resection.

Clinical Trials as Topic↗