YUMM1.7 Syngeneic Model Service for Melanoma

The YUMM1.7 syngeneic model is the defined-genotype, checkpoint-refractory melanoma platform, engrafting a BRAF V600E/PTEN-null/CDKN2A-null murine melanoma — born in Yale's genetically engineered mouse program — into syngeneic C57BL/6 hosts where genuine anti-PD-1 resistance creates the ideal proving ground for next-generation immunotherapy combinations. Alfa Cytology delivers this modern benchmark as a complete preclinical service — authenticated cell banking from the 2014 Yale reference, low-inoculum subcutaneous implantation, checkpoint and BRAF-inhibitor benchmarking, tumor-microenvironment reprogramming arms, and full histopathology — giving sponsors the human-relevant genetics and documented resistance phenotype that B16-derived models cannot supply.

Overview of YUMM1.7 Syngeneic Model for Melanoma

YUMM1.7 belongs to the Yale University Mouse Melanoma series, created by Marcus Bosenberg's laboratory to answer a deceptively simple question: what does a melanoma with the genetics of the human disease actually look like in a mouse? Established in 2014 from a 4-hydroxytamoxifen-induced tumor in a male C57BL/6 mouse and characterized in the landmark 2016 Meeth paper that introduced the whole YUMM panel, the line carries the three alterations most frequently found in human cutaneous melanoma — a heterozygous BRAF V600E driver, homozygous PTEN deletion, and CDKN2A knockout — a defined genotype in stark contrast to the chemically induced, genetically opaque B16 family that had dominated murine melanoma research for decades. The series was explicitly designed as congenic partners to the genetically engineered mice from which they sprang, and YUMM1.7 is among its fastest members: 10⁵ subcutaneous cells in C57BL/6 hosts reach 1 cm³ within roughly five weeks, compressing timelines that the corresponding Braf/Pten/Cdkn2a GEMM needs six to eight weeks to deliver.

Fig 1. Tumor growth curves of YUMM1.7 in immunocompetent C57BL/6 versus immunodeficient NSG mice with mathematical modeling of intrinsic proliferation (kP) and immune-mediated cell death (kD), revealing minimal immune selective pressure in the YUMM1.7 syngeneic model. (Klinke, David J., et al., 2025)

It is the immunology, though, that has made YUMM1.7 indispensable. The line is poorly immunogenic in the most rigorous sense — tumors grow identically in wild-type and RAG1-deficient hosts, proving the adaptive immune system neither rejects nor restrains it — and its microenvironment is macrophage-dominated, with 35–45% of intratumoral nucleated cells being CD45⁺ leukocytes of which the great majority are F4/80⁺ tumor-associated macrophages, while fewer than 1% of intratumoral leukocytes are CD3⁺ T cells. Repeated studies have shown no antitumor activity of anti-PD-1 or anti-PD-L1 against YUMM1.7, making it — alongside YUMM1.1 and B16 — the canonical checkpoint-refractory melanoma, and therefore the preferred substrate for resistance-breaking science. The literature has obliged with landmark demonstrations: depleting the histone demethylase KDM5B rewires retroelement expression and renders YUMM1.7 sensitive to anti-PD-1, and YAP1 inhibition with verteporfin synergizes with anti-PD-1 in YUMM1.7 (but not in B16-F10) by pushing the microenvironment toward an inflamed, T-cell-and-M1-macrophage-rich state. The line also reproduces the clinical BRAF-inhibitor narrative faithfully — PLX4720 chow halts growth until about day 50, whereupon resistant growth emerges — and its UVB-irradiated derivative YUMMER1.7 layers ultraviolet-driven mutational burden onto the same genotype for immunogenicity comparisons. For sponsors attacking checkpoint resistance, macrophage biology, or BRAF-pathway escape, YUMM1.7 is the most human-relevant murine melanoma available.

Cell Line Information: YUMM1.7 Syngeneic Model

YUMM1.7 (Cellosaurus CVCL_JK16) is the BRAF V600E/PTEN-null/CDKN2A-null line of the Yale University Mouse Melanoma series, established in 2014 and characterized in Meeth et al. (2016), distributed within the melanoma research community with authenticated provenance. The UVB-mutagenized YUMMER1.7 derivative (CVCL_A2AX) extends the platform for mutational-burden studies. Core characteristics are compiled below.

Our Services

Engaging Alfa Cytology for the YUMM1.7 syngeneic model places the most human-relevant murine melanoma under one accountable team: authenticated YUMM1.7 banks are maintained at low passage with the line's defined genotype verified, syngeneic C57BL/6 hosts are sourced and acclimated, tumors are established at the low 10⁵-cell inoculum that delivers ~5-week kinetics, and treatment arms — checkpoint blockade benchmarks expected to confirm refractoriness, BRAF/MEK-pathway regimens with resistance kinetics, macrophage-targeting or microenvironment-reprogramming strategies, and KDM5B/YAP1-pathway mechanistic arms — run through scheduled caliper monitoring to terminal histopathology with immune-marker panels, all under IACUC-compliant conditions and returned as an audit-ready data package.

Workflow of YUMM1.7 Syngeneic Model Construction

YUMM1.7 studies are built around its two documented personalities — the checkpoint-refractory immunotherapy substrate and the BRAF-inhibitor response/resistance model — both resting on the low-inoculum kinetics the founding paper established. A standard program proceeds as follows.

1. Cell preparation and quality control: YUMM1.7 cells are expanded at low passage, confirmed mycoplasma-free, and genotype spot-checked against the BRAF V600E/PTEN-null/CDKN2A-null reference; suspensions are prepared fresh at the 10⁵-cell inoculum.
2. Host selection and acclimation: Male or female C57BL/6 mice, typically 6–10 weeks of age, are quarantined and acclimated in a specific-pathogen-free barrier facility.
3. Implantation: subcutaneous route. 10⁵ cells in 0.1 mL sterile PBS are injected into the flank; the site is compressed briefly on needle withdrawal, and tumors follow the documented trajectory toward 1 cm³ within approximately five weeks.
4. Randomization and checkpoint benchmarking: Mice are randomized by tumor volume into arms; anti-PD-1 (clone RMP1-14) or anti-PD-L1 (clone 10F.9G2) benchmark arms run in parallel with test articles to confirm the documented refractory baseline before combination strategies are judged.
5. BRAF-pathway arms where specified: For targeted-therapy questions, BRAF inhibitors (e.g., PLX4720 dietary or formulated dosing) are initiated one week post-implantation per the published kinetics, with growth tracked through the response phase to documented escape.
6. Resistance-breaking and microenvironment arms. Test modalities: KDM5B-pathway interventions, YAP1 inhibition, macrophage-targeting agents, STING or innate agonists — are dosed per protocol, with combination anti-PD-1 arms where sensitization is the question.
7. Longitudinal monitoring: Tumors are measured by caliper twice weekly; luciferase-tagged cohorts where deployed undergo bioluminescence imaging after intraperitoneal D-luciferin injection, and body weight and clinical signs are recorded daily.
8. Endpoint analysis and reporting: At termination, tumors are resected and weighed; tissues undergo H&E with melanoma histology, immunohistochemistry (CD8, CD4, FoxP3, F4/80, CD31, PD-L1, YAP1 panels), flow-cytometric tumor-infiltrating-leukocyte profiling quantifying the documented macrophage dominance and T-cell sparsity, and metastatic-organ screening, with all data consolidated into the final report.

Fig 2. YUMM1.7 Syngeneic Model construction workflow.

Case Study-YUMM1.7 Syngeneic Model

Alfa Cytology has applied the YUMM1.7 syngeneic platform to preclinical programs spanning checkpoint resistance mechanisms and overcoming strategies, BRAF/MEK-pathway response and escape kinetics, macrophage-targeting therapies, and tumor-microenvironment reprogramming in melanoma. In these engagements, caliper and bioluminescence readouts tracked the documented growth kinetics, checkpoint benchmark arms confirmed the refractory baseline, and terminal histopathology with immune-marker panels and flow-cytometric tumor-infiltrating-leukocyte profiling completed the pharmacological and immunological assessment. Study parameters — inoculum, treatment arms, monitoring cadence, and endpoint panels — are tailored to each program. Case materials can be shared under confidentiality agreements upon request.

Why Choose Alfa Cytology?

YUMM1.7 demands more of a CRO than a flank tumor: it requires genotype literacy, checkpoint-refractory benchmark discipline, and macrophage-biology fluency. Alfa Cytology fields these capabilities in-house, making the YUMM1.7 syngeneic model a dependable backbone for your melanoma program.

• Defined human-relevant genotype — BRAF V600E, PTEN-null, CDKN2A-null — verified by spot-check.
• Canonical checkpoint-refractory phenotype, with anti-PD-1/PD-L1 benchmark arms run natively.
• Low-inoculum kinetics, deploying the published 10⁵-cell geometry for ~5-week timelines.
• BRAF-inhibitor kinetics expertise, tracking response to the documented ~day-50 escape window.
• Resistance-breaking precedent fluency, including KDM5B and YAP1-pathway strategies.
• Macrophage-biology depth, quantifying the documented TAM-dominated, T-cell-sparse microenvironment.
• IACUC-compliant, documentation-rich operations delivering audit-ready records throughout the study.

Contact Us

If your melanoma program targets checkpoint resistance, BRAF-pathway escape, or macrophage biology, contact us today to discuss YUMM1.7 study design, benchmark arms, and endpoint strategy with our scientific team. Reach out for a confidential consultation and project quotation — Alfa Cytology looks forward to advancing your next preclinical study.

For research use only. Not intended for any clinical use.