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PubMed1975

Properties of bispecific rosette-forming cells. I.--Presence of T-lymphocyte markers.

Three T-cell markers have been used to determine the origin of bispecific rosette forming cells (RFC) observed after stimulation by two species of heterologous red cells. The inhibition by anti-theta serum (AOS), azathioprine (AZ) and anti-lymphocyte serum (ALS) of the majority of bispecific RFC indicates their T-cell origin. The study of their sensitivity to these inhibitors suggested that about half of the bispecific RFC belong to immature T1 cell subset and the other half to more mature T2 cells. Conversely, monospecific RFC include both B-celle RFC have characteristics different from monospecific RFC argues against the reaction of double RFC against a common antigenic determinant of the two erythrocyte types.

Animals↗
PubMed2025

Missense variants in human forkhead transcription factors reveal determinants of forkhead DNA bispecificity.

Recognition of specific DNA sequences by transcription factors (TFs) is a key step in transcriptional control of gene expression. While most forkhead (FH) TFs bind either an FKH (RYAAAYA) or an FHL (GACGC) recognition motif, some FHs can bind both motifs. Mechanisms that control whether an FH is monospecific vs. bispecific have remained unknown. Screening a library of 12 reference FH proteins, 61 naturally occurring missense variants including clinical variants, and 22 designed mutant FHs for DNA-binding activity using universal ("all 10-mer") protein-binding microarrays revealed non-DNA-contacting residues that control mono- vs. bispecificity. Variation in non-DNA-contacting amino acid residues of TFs is associated with human traits and may play a role in the evolution of TF DNA-binding activities and gene regulatory networks.

Humans↗
PubMed2026

MET-Aberrant non-small cell lung cancer: from kinase dependence to cell-surface targetability-mechanistic basis and biomarker framework for bispecific antibodies and antibody-drug conjugates.

MET-aberrant non-small cell lung cancer (NSCLC) is not a uniform therapeutic entity. Its biology, diagnostic pathways, and treatment sensitivity differ across MET exon 14 skipping alteration (METex14), MET amplification, and MET overexpression. This heterogeneity cannot be fully explained by conventional event-based classification and is reflected in the distinct clinical activity of MET tyrosine kinase inhibitors (MET-TKIs), bispecific antibodies (BsAbs), and antibody-drug conjugates (ADCs). With the emergence of antibody-based therapies, MET has evolved from a signaling driver to a cell-surface target for receptor modulation and payload delivery. We therefore propose a clinically anchored two-dimensional framework for interpreting therapeutic relevance in MET-aberrant NSCLC: kinase dependence and cell-surface targetability. Neither dimension should be regarded as a directly measurable binary variable. Kinase dependence is inferred from genomic and treatment-contextual proxies, most strongly METex14 and, more conditionally, high-level focal MET amplification. Cell-surface targetability is approximated by drug-specific IHC assessment of assay-defined c-MET protein expression; however, receptor internalization, intracellular trafficking, and payload delivery capacity remain incompletely measurable in routine clinical practice. Within this framework, MET-TKIs have the most evidence-supported established role in tumors with evidence of MET-driven kinase dependence. EGFR × MET BsAbs have demonstrated clinical activity in broad post-osimertinib EGFR-mutant NSCLC, while EGFR/MET co-dependence or MET-mediated bypass activation provides a mechanistic rationale for their use; MET-defined preferential benefit remains to be prospectively established. MET-directed antibody-drug conjugates (MET-ADCs) are supported in drug- and assay-defined populations with high c-MET protein overexpression, although the predictive relevance of delivery-related factors remains hypothesis-generating. Accordingly, MET testing should shift from single-event detection to platform-oriented stratification: next-generation sequencing (NGS) for driver alterations and resistance profiles, fluorescence in situ hybridization (FISH) for high-level focal amplification, and immunohistochemistry (IHC) for surface expression relevant to antibody-based therapies. This framework is intended to organize current biological and clinical evidence rather than to replace drug-specific companion diagnostics, regulatory indications, or prospectively validated treatment-selection algorithms. Precision treatment of MET-aberrant NSCLC is thus moving from event-based drug selection toward mechanism-based therapeutic matching. Future priorities include standardizing biomarkers, defining optimal target populations, and aligning biological subtypes, diagnostic strategies, and therapeutic platforms.

Antibody-drug conjugate↗
PubMed2026

Real-World Efficacy and Safety of Standard-of-Care Chimeric Antigen Receptor T-Cell (CART) and Bispecific T-Cell Engager (TCE) Therapies in Relapsed/Refractory Multiple Myeloma (RRMM).

We aimed to evaluate the real-world (RW) efficacy and safety of standard-of-care CART versus TCE therapies in relapsed/refractory myeloma (RRMM), to assess utilization, outcomes, and tolerability of these therapies in a RW oncology in the US. Data were derived from the US-based, electronic health record-derived deidentified Flatiron Health Research Database, 2021-2024. A total of 419 patients (CART n = 220; TCE n = 199) with a confirmed diagnosis of myeloma who received CART or TCE as a standard-of-care treatment after at least 2 prior lines of therapy were included. Patients in the CART cohort were younger, had better ECOG PS, and a higher receipt of a prior autologous stem cell transplant versus bispecific TCE cohort. In CART versus TCE cohort, the overall response rates (ORR) were 83.3% versus 66.3%, median duration of response 7.9 months versus 4.3 months, progression free survival (PFS) 13.6 months versus 10.5 months, and overall survival (OS) of 29.8 months versus 21.9 months, respectively. A higher percentage of hematologic toxicity, infections, and cytokine release syndrome (CRS) were noted in the CART versus TCE cohort. This study provides insights on the RW effectiveness of CART versus TCE in the treatment of RRMM; highlights the differences in patient selection, clinical responses, treatment duration, and toxicity profiles.

CART↗
PubMed1975

The potentiality of antibody-producing cells. II. Evidence for two antibody molecules of different specificities secreted by micromanipulated bispecific mouse spleen cells.

Bispecific PFC appearing on the 4th day after immunization of mice with sheep erythrocytes conjugated with trinitrophenyl hapten (TNP-SRBC) were identified by their capacity to lyse native SRBC and TNP-conjugated horse erythrocytes (TNP--HoRBC) simultaneously in an open carboxymethylcellulose medium. Individual PFC thus detected, were micromanipulated into two successive media containing the indicators SRBC and TNP--HoRBC. Out of 103 transferred double cells ninety-two (89 per cent) remained double in the second medium and of the ninety-two transferred into the third medium, fifty-four (58 per cent) provoked a double lysis, eighteen (19 per cent) provoked a single lysis and twenty (23 per cent) ceased to lyse. On the other hand, when the second medium contained the indicators and the soluble specific inhibitor (TNP--BSA), out of 156 transferred double PFC, 125 (80 per cent) became single and only nineteen (12 per cent) remained double. Of these cells, 136 were transferred into the third medium (not containing inhibitor) and here again sixty-five (48 per cent) became double, forty-nine (36 per cent) remained single and twenty-two (17 per cent) ceased to provoke any lysis. Other double PFC were micromanipulated from the original revealing medium into two successive media containing only one indicator and the homologous (second medium) or the heterologous third medium) soluble inhibitor (TNP--BSA or soluble SRBC antigen), in order to see whether a soluble inhibitor suppresses only the corresponding specific lysis. Out of 186 double PFC transferred into the media containing the indicator and the corresponding inhibitor 147 (79 per cent) were specifically inhibited, whereas out of 176 double PFC transferred into the third medium (in which about 20 per cent of the cells cease to function) containing one indicator and the unrelated inhibitor, 117 (66-6 per cent) lysed the indicator in spite of the presence of the unrelated inhibitor. Since a specific inhibitor suppresses the lysis of the corresponding indicator, whereas its presence does not interfere with the lysis of the unrelated indicator in the majority of double PFC, it can be concluded that these cells secrete two types of antibody molecules possessing different specificities.

Animals↗
PubMed2026

Integrated molecular and immune profiling identifies FOXA1 as a complementary co-target to MUC1 for bispecific immunotherapy in breast cancer.

In breast cancer immunotherapy, Mucin 1 (MUC1) is a well-established target with promising preclinical results; however, single targeting of MUC1 has demonstrated limited efficacy in clinical trials, largely due to tumor heterogeneity, diverse glycosylation patterns, and an immunosuppressive TME. Identification of complementary co-targets enables bi-specific or dual-target immunotherapy, limiting antigen escape, improving specificity, and reducing relapse. Here, we employed a comprehensive multi-layered analytical approach to evaluate MUC1 expression, clinical relevance, and methylation status, followed by systematic screening of MUC1-correlated genes. Antigenicity prediction and protein-protein interaction analyses identified Forkhead Box A1 (FOXA1) as a potential functional partner. Expression analysis revealed concordant patterns of MUC1 and FOXA1 across breast cancer samples, while network mapping demonstrated shared interactions with adhesion-associated proteins, including CTNNB1, CTNND1, and CDH1, suggesting roles in epithelial organization and tumor progression. Further validation using gene expression datasets from Indian breast cancer cohorts confirmed consistent expression and correlation patterns, supporting reproducibility across populations. Immune profiling revealed an inverse association between MUC1-FOXA1 co-expression and immune-related gene signatures, with high co-expression linked to reduced infiltration of dendritic cells, CD4⁺ and CD8⁺ T cells, macrophages, and natural killer cells, indicative of an immunosuppressive microenvironment. Negative correlations with MHC Class I genes further suggested impaired antigen presentation. Epitope prediction identified high-affinity peptides from both targets with strong MHC Class I binding potential. Collectively, these findings support the associated role of MUC1 and FOXA1 as dual immunotherapeutic targets in breast cancer.

Hepatocyte Nuclear Factor 3-alpha↗
PubMed1975

Properties of bispecific rosette-forming cells. II. --Rosette formation by "educated" T-lymphocytes.

Normal thymus cells transferred into thymectomized and lethally irradiated syngeneic mice responded to stimulation with sheep erythrocytes by rosette formation with these erythrocytes. This response reached a peak on the 7th day and was not associated with any production of circulating antibodies. Rosettes produced by "educated" T-cells were inhibited by anti-theta serum as well as by anti-mouse Fab serum. Simultaneous stimulation of transferred thymocytes with sheep and pigeon erythrocytes provoked the appearance of a minority of cells simultaneously binding both types of erythrocytes. Depletion of B cells contaminating normal thymocyte populatins after passage through anti-mouse Ig coated columns before their transfer in thymectomized and irradiated recipients did not prevent the appearance of simple and double RFC. Moreover, when normal thymocytes or T-cells "educated" by allogeneic stimulation were incubated at 4 degrees C with anti-SRBC and anti-PRBC mouse sera a subsequent incubation at 37 degress of resulted in the dissociation of most passive rosettes formed at 4 degrees. Conversely similar incubation at 37 degrees of rosettes formed by actively immunized cells resulted in capping of about 50% simple and double rosettes. This redistribution of membrane receptors is proposed as a routine test for distinguishing active from passive rosettes.

Animals↗
PubMed2025

Proximity between LAG-3 and the T cell receptor guides suppression of T cell activation and autoimmunity.

Therapeutically targeting pathogenic T cells in autoimmune diseases has been challenging. Although LAG-3, an inhibitory checkpoint receptor specifically expressed on activated T cells, is known to bind to major histocompatibility complex class II (MHC class II), we demonstrate that MHC class II interaction alone is insufficient for optimal LAG-3 function. Instead, LAG-3's spatial proximity to T cell receptor (TCR) but not CD4 co-receptor, facilitated by cognate peptide-MHC class II, is crucial in mediating CD4+ T cell suppression. Mechanistically, LAG-3 forms condensate with TCR signaling component CD3ε through its intracellular FSAL motif, disrupting CD3ε/lymphocyte-specific protein kinase (Lck) association. To exploit LAG-3's proximity to TCR and maximize LAG-3-dependent T cell suppression, we develop an Fc-attenuated LAG-3/TCR inhibitory bispecific antibody to bypass the requirement of cognate peptide-MHC class II. This approach allows for potent suppression of both CD4+ and CD8+ T cells and effectively alleviates autoimmune symptoms in mouse models. Our findings reveal an intricate and conditional checkpoint modulatory mechanism and highlight targeting of LAG-3/TCR cis-proximity for T cell-driven autoimmune diseases lacking effective and well-tolerated immunotherapies.

Animals↗
PubMed2026

Pre-treatment T cell features and immune-milieu characteristics shape treatment-induced exhaustion and resistance to Blinatumomab in B-cell acute lymphoblastic leukemia.

BACKGROUND: Blinatumomab (Blina), a CD19×CD3 bispecific T cell engager, is approved for the treatment of B-cell precursor acute lymphoblastic leukemia (BCP-ALL), yet resistance remains a major challenge and the mechanisms driving treatment failure remain poorly understood. METHODS: To define the immunological determinants of resistance, we performed longitudinal profiling of peripheral blood T cells and the immune milieu of 34 patients receiving Blina using flow cytometry (n=19), single-cell CITE-seq (n=13), ex vivo Blina-induced cytotoxicity (n=26) and serum proteomics (n=17). RESULTS: At baseline, Responders (R) were enriched for CD8+ effector memory T cells (TEM) expressing higher levels of cytotoxic genes and their transcriptional regulator ZNF683. Conversely, CD8+ TEM from Non-Responders (NR) displayed transcriptional features of activation without proportionate cytotoxic commitment. Over the course of the first treatment cycle, NR exhibited a progressive expansion of TIM3+CD8+ T cells that correlated with a rapid loss of ex vivo cytotoxic function. Linking baseline state to post-treatment T-cell exhaustion, the magnitude of TIM3+CD8+ expansion correlated inversely with baseline ZNF683 expression in CD8+TEM. Beyond T-cell-intrinsic features, NR harbored an immunosuppressive milieu characterized by higher circulating levels of M2-polarizing factors (CSF-1, HGF) and the TIM-3 ligand Galectin-9, which correlated positively with the magnitude of TIM3+CD8+ T-cell expansion. CONCLUSIONS: These findings indicate that post-Blina CD8+ T-cell exhaustion is associated with resistance and it is shaped by both reduced ZNF683-dependent cytotoxic programming in CD8+ TEM and an immunosuppressive milieu. This provides a rationale for risk stratification based on baseline transcriptional profiling of CD8+ TEM and for combinatorial strategies targeting the suppressive microenvironment.

Humans↗
PubMed2025

Intracranial and systemic progression on amivantamab in platinum-treated epidermal growth factor receptor exon 20 insertion-mutated advanced non-small cell lung cancer.

BACKGROUND: Amivantamab, an epidermal growth factor receptor (EGFR)-MET bispecific antibody, is approved as monotherapy and as combination therapy for patients with advanced non-small cell lung cancer (NSCLC) harboring various EGFR mutations in first-line and refractory settings. Sites of progressive disease on amivantamab monotherapy are not well understood and could be instructive for treatment management. METHODS: CHRYSALIS (NCT02609776) enrolled participants with NSCLC, including those with treated brain metastases. Brain magnetic resonance imaging was required at screening but performed per local practice after enrollment (conducted postbaseline every 6 [±1] weeks after Cycle 1 Day 1). Sites of target, non-target, and new lesion progression were reported. This analysis includes 114 participants with EGFR exon 20 insertion (Ex20ins) NSCLC after disease progression on platinum-based chemotherapy who received amivantamab monotherapy on or before June 4, 2020. RESULTS: As of March 30, 2021, the median follow-up was 12.5 months (range, 0.2-30.5). Among 114 participants, the objective response rate by blinded independent central review was 43 %; median duration of response was 10.8 months, and median progression-free survival was 6.7 months. RECIST-defined progressive disease occurred in 72/114 participants (63 %); 25/72 (35 %) continued amivantamab after progression (4.2 median additional months; range, 1.0-12.5). The most common first sites of progression were the lungs/pleura (29 %), followed by bone (21 %), brain (15 %), and lymph node (12 %). Thirteen participants (11 %) had intracranial-only first progression. Six of these 13 participants underwent stereotactic radiosurgery (SRS) while continuing amivantamab. The median duration of amivantamab treatment post-progression in these 6 participants was 4.0 months (range, 2.3-6.0). SRS was well tolerated, with 2 adverse events reported (nausea and fatigue, n = 1 each). CONCLUSIONS: Amivantamab monotherapy in post-platinum Ex20ins NSCLC demonstrated meaningful antitumor activity in participants, and intracranial-only progression was infrequent. Treatment of brain progression with SRS while continuing amivantamab appears feasible and tolerable.

Adult↗
PubMed2026

Blinatumomab for Replacing Chemotherapy in Pediatric Acute Lymphoblastic Leukemia.

BACKGROUND: Blinatumomab, a bispecific T-cell engager targeting the CD19 antigen on B cells, may offer an option to safely replace cycles of traditional chemotherapy in pediatric patients with newly diagnosed high-risk B-cell acute lymphoblastic leukemia (ALL). METHODS: We randomly assigned, in a 1:1 ratio, children with high-risk B-cell ALL to receive two cycles of blinatumomab (blinatumomab group) or two cycles of chemotherapy (control group) after consolidation. The primary end point was event-free survival as evaluated in a time-to-event analysis; the duration of event-free survival was defined as the time from randomization to the first event among resistance to protocol treatment, relapse, second cancer, or death from any cause. Our primary objective was to evaluate whether the 4-year event-free survival would be 10 percentage points higher in the blinatumomab group than in the control group. RESULTS: Overall, 709 of 768 eligible patients (92.3%) underwent randomization; 358 were assigned to the blinatumomab group and 351 to the control group. A planned interim analysis at a median follow-up of 2.9 years showed an estimated 4-year event-free survival of 83.0% (95% confidence interval [CI], 77.4 to 87.4) in the blinatumomab group and 70.3% (95% CI, 63.8 to 75.9) in the control group (P&#x2009;=&#x2009;0.0002 in an intention-to-treat analysis). The estimated hazard ratio for a primary end-point event (blinatumomab vs. control) was 0.51 (95% CI, 0.35 to 0.73) as assessed with a Cox model. Infection related to the trial treatment occurred in 23.9% of patients in the blinatumomab group and in 69.4% of those in the control group (P<0.001). Life-threatening adverse events occurred in 2 patients (0.5%) in the blinatumomab group, including one (in 0.3%) that was fatal, and in 16 patients (4.7%) in the control group. Neurotoxic events were reported in 12.0% and 3.2%, respectively (P<0.001). Cytokine release syndrome of grade 2 or higher occurred in 1.1% of patients in the blinatumomab group. CONCLUSIONS: In children with newly diagnosed high-risk B-cell ALL, replacement of two cycles of highly toxic conventional chemotherapy with blinatumomab resulted in a significantly greater percentage of patients with event-free survival at 4 years. (Funded by Deutsche Krebshilfe and others; AIEOP-BFM ALL 2017 EudraCT number, 2016-001935-12; EU Clinical Trials number, 2023-509856-32-00; and ClinicalTrials.gov number, NCT03643276.).

Adolescent↗
PubMed2026

Treatment Decisions in Multiple Myeloma.

Revolutions in transplantation and targeted and immune therapies have transformed multiple myeloma from a disease with an associated survival of a few years into one for which functional cure is an emerging goal. This abundance of effective therapies has created clinical complexity. Here we provide a practical framework, anchored in trial evidence and informed by emerging biologic discoveries, for the navigation of treatment decisions across the disease spectrum. We outline how cytogenetic and genomic risk stratification, functional fitness, and measurable residual disease status individualize therapy in newly diagnosed disease, in which quadruplet induction therapy is now standard and the role of autologous transplantation is being reevaluated. Regarding relapse, we address the sequencing of B-cell maturation antigen-directed chimeric antigen receptor (CAR) T cells, bispecific antibodies, and antibody-drug conjugates, emphasizing T-cell fitness and multiantigen targeting to counter exhaustion and antigen escape. We also consider early interception in high-risk smoldering myeloma. Throughout, we underscore that enrollment of patients in clinical trials should be considered in order to ensure continued progress.

Humans↗
PubMed2026

Amivantamab in Recurrent/Metastatic Head and Neck Squamous Cell Cancer After Checkpoint Inhibitor and Chemotherapy: Pivotal Results From the Phase Ib/II OrigAMI-4 Study.

Single-agent paclitaxel or cetuximab after immune checkpoint inhibitor (ICI) and chemotherapy demonstrated objective response rates (ORRs) of 21%-24% in recurrent/metastatic (R/M) head/neck squamous cell cancer (HNSCC). Epidermal growth factor receptor (EGFR) and MET are overexpressed in R/M HNSCC. Amivantamab, an EGFR-MET bispecific antibody, may be a rational treatment. Cohort 1 of OrigAMI-4 (ClinicalTrials.gov identifier: NCT06385080) evaluated subcutaneous amivantamab administered every 3 weeks in participants with non-human papillomavirus R/M HNSCC after PD-(L)1 inhibitor and platinum-based chemotherapy. Prior anti-EGFR therapy and p16-positive oropharyngeal cancer were exclusionary. The primary end point was RECIST v1.1 ORR. Secondary end points included duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. In 102 participants, blinded independent central review&#x2011;assessed ORR was 42% (95% CI, 32 to 52); the complete response rate was 15%. Median DoR was not reached (NR; 95% CI, 6.9 to NR); 56% of responses lasted &#x2265;6 months. Investigator-assessed ORR was 47% (95% CI, 37 to 57). At a median follow-up of 11.8 months (range, 1.1-21.9), median PFS and OS were 6.8 months (95% CI, 5.2 to 8.3) and 12.5 months (95% CI, 10.2 to 16.8), respectively. Adverse events were consistent with previous experience with no new safety signals. Treatment-related discontinuations were low (8%). Amivantamab demonstrated greater antitumor activity in participants previously exposed to ICI and chemotherapy than has been reported for paclitaxel or cetuximab.

Humans↗
PubMed2026

Immunological Features of Neuroendocrine Neoplasms and Adrenal Tumors.

Neuroendocrine neoplasms, which occur throughout the human body, as well as adrenocortical carcinoma and pheochromocytoma, which originate in the adrenal gland, are primarily classified as rare malignancies. Immunotherapy, including immune checkpoint inhibitors (ICIs), is generally not incorporated into the standard care protocols for these tumors. The clinical efficacy of ICIs in these tumors has been modest. This may be due to the biological heterogeneity of these tumors. The tumor immune microenvironment profiles are heterogeneous among the molecular subtypes of pheochromocytoma/paraganglioma, suggesting a potential benefit observed in selected subgroups. Poorly differentiated neuroendocrine carcinoma (NEC) exhibits spontaneous activation of adaptive immunity, unlike well-differentiated neuroendocrine tumors. A delta-like ligand 3-directed T-cell-engaging bispecific antibody, tarlatamab, has recently demonstrated prolonged survival in small cell lung cancer, and investigations into its use in extrapulmonary NEC are underway. This review examines the immunological features of representative neuroendocrine and adrenal tumors (neuroendocrine tumor, neuroendocrine carcinoma, adrenocortical carcinoma, and pheochromocytoma/paraganglioma). In the future, elucidating the relationship between specific molecular subtypes and immunophenotypes may facilitate the development of personalized therapies and guide clinical investigations in promising patient subpopulations.

Humans↗
PubMed2026

Novel immunotherapeutic strategies for colorectal cancer treatment: Advances, challenges, and future directions.

Immunotherapy has reshaped the treatment landscape of colorectal cancer (CRC), with the clearest and most durable benefit established in mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) disease. However, framing CRC immunotherapy simply as "MSI-H responsive versus microsatellite stable (MSS) resistant" is no longer sufficient. Recent studies indicate that a subset of proficient mismatch repair (pMMR) colon cancers, particularly in the neoadjuvant setting, can mount clinically meaningful responses to immune checkpoint blockade, suggesting that disease stage, local immune organization, and treatment timing critically influence immunotherapy sensitivity. In parallel, emerging evidence has expanded the relevant immune landscape beyond the tumor bed itself, showing that spatially organized stromal and adipose niches can actively divert tumor-reactive lymphocytes and promote immune escape. These advances shift the central challenge in CRC immunotherapy from simply identifying new agents to defining when and in whom immune resistance is reversible, and which biological bottlenecks-such as vascular dysfunction, myeloid suppression, and spatial immune exclusion-must be overcome. In this context, alternative checkpoint inhibitors, bispecific antibodies, cellular therapies, vaccines, nanotechnology-enabled platforms, and microbiome-targeted approaches remain important, but their translational maturity and evidentiary support differ substantially. Biomarker development is likewise evolving from static genomic classification toward dynamic and mechanism-informed stratification incorporating circulating tumor DNA (ctDNA), chromosomal instability, immune architecture, and treatment-induced response trajectories. This review synthesizes recent advances in CRC immunotherapy while emphasizing evidence hierarchy, biomarker-guided patient selection, and the mechanistic basis of combination strategies. We argue that the next phase of CRC immunotherapy will depend less on the indiscriminate addition of novel agents and more on the rational deployment of immunotherapy across molecularly, spatially, and temporally defined disease states.

Humans↗