GigaMune

Cancer evolves. One dose does not cure it.

In vivo CAR-T works, and every lentivector in the clinic pseudotypes with a close variant of VSV-G. That makes the second dose the hard problem, because the immune response raised by the first one is waiting for it. GigaMune holds hundreds of unrelated pseudotypes.

Kaplan-Meier survival curve. Mice receiving an anti-CD19 CAR delivered in vivo remain at 100 percent survival through day 41, while untreated and GFP-only control cohorts decline from day 20.
Complete tumor clearance in mice Survival following in vivo delivery of an anti-CD19 CAR by a GigaMune pseudotype (treated) against untreated and transgene-only controls (). Reproduced from US 12,371,689 B2, Fig. 9.

In vivo CAR-T matured in about twelve months

Lentivector in vivo CAR-T has shown promising efficacy in early clinical studies, and the market has priced it accordingly: Interius, EsoBio and Kelonia were all acquired inside the last year, for sums running from hundreds of millions into the billions.

The field is treating a single dose as sufficient

Current programs assume one dose can clear a tumor, and newer entrants assume any shortfall can be engineered away with armored or dual-targeted constructs. Almost every other anti-tumor pharmaceutical is dosed more than once, for the obvious reason: relapse rates after anti-CD19 and anti-BCMA CAR-T run 50 to 60 percent because the disease adapts.

A second dose of VSV‑G is unlikely to work

The first dose is immunogenic. By the time a second is warranted, anti-vector antibodies are circulating, and a vector that differs from the first by a few residues will not evade them. Redosing is not a formulation problem. It is a sequence-identity problem.

Pseudotype diversity is the way through

Our patented pseudotypes average 40 percent sequence identity to VSV-G — different enough that prior exposure to one says nothing about the next. That makes sequential dosing tractable in three directions at once: different CARs in sequence, booster doses against escape clones, and local intratumoral delivery.

We went looking in unannotated sequence data

Starting from roughly a thousand envelope proteins covering the known enveloped RNA viruses, we searched terabases of unannotated sequence using Serratus, a cloud-scale alignment method. The diversity that came back is the asset.

Nine surface proteins were carried into wet lab screening. Sequence identity across them ranges from 26 to 85 percent, and predicted structure is conserved throughout — divergent enough to evade prior immunity, conserved enough to work.

9,260 novel viral envelope proteins identified
166 with detectable similarity to VSV-G
40% average sequence identity to VSV-G across our pseudotypes
Predicted structures of VSV-G and nine candidate envelope proteins. All nine share the same three-domain fold; residues differing from VSV-G are coloured red.
Predicted structures for VSV-G and the nine candidates carried into screening. Residues identical to VSV-G are white; everything divergent is red. Sequence identity across the set runs from 26 to 85 percent, yet the fusion, pleckstrin homology and trimerization domains sit in the same relative positions throughout, with Cα deviations of 0.25 to 2.1 Å.

US 12,371,689 B2

Engineered enveloped vectors and methods of use thereof. Issued 29 July 2025 to GigaMune, Inc.

The portfolio covers engineered enveloped vectors combining a viral envelope protein with a targeting moiety, and the methods for making and using them. It is the basis of our claim to redosing, and it is why pseudotype diversity is a position rather than an observation.

First page of United States Patent 12,371,689 B2, Engineered enveloped vectors and methods of use thereof, assigned to GigaMune, Inc.

Non-dilutive funding

GigaMune has won seven Phase I SBIR awards from the National Cancer Institute, the National Institute of Allergy and Infectious Diseases, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases, together with a Fast Track SBIR funded through Phase II, supporting in vivo work on anti-tumor TCRs in melanoma.

Two founders

David Johnson, Ph.D.

David Johnson, Ph.D.

Founder and President
  • Ph.D. Genetics, Stanford
  • Founding COO, Natera
  • Founder and CEO, GigaGen — acquired by Grifols
  • PI on multiple NIH SBIR awards
Matthew Spindler, Ph.D.

Matthew Spindler, Ph.D.

Founder and VP Research
  • Ph.D. Pharmaceutical Sciences, UCSF
  • Postdoc in T cell immunology, Stanford
  • Director of Cell Engineering, GigaGen
  • PI on four GigaMune SBIRs — three NCI, one NIAID
  • First author, 2020 Nature Biotechnology paper on TCR discovery

Advisors

Robert Edgar, Ph.D.
Sequence algorithms; author of Serratus (Nature, 2022)
Everett Meyer, M.D., Ph.D.
Clinical cell therapy, Stanford

Talk to us

We are interested in conversations with investors, potential partners in cell therapy, and scientists who want to work on vector immunity.

info@gigamune.com