Immunotherapy: ch14.18 vs antibody-3F8

(Sam Saffron) #1

Usage of ch14.18 is ubiquitous these days in Neuroblastoma treatment, yet Memorial Sloan Kettering continue to treat patients with 3f8 (in addition it seems this treatment is available in Hong Kong)

There is some information here: which seems a bit old.

The reasoning there is that, in theory, in some cases you can get more doses of 3f8 which in turn would allow you a better chance.

This leads me to a few questions:

  • Is there any current studies comparing the 2?
  • If you already had ch14.18 can you follow on with 3F8 treatment?
  • Why is 3F8 only available in Sloan (and HK)?

hu3F8 available in Hospital Sant Joan Déu in Spain (and other hospitals)
(Rochelle Paterson) #2

I had similar questions. The following is a link to the only comparison I’ve ever read on the 2 antibodies, but it’s very dated and may be insignificant now since it was before 3F8 was humanized and was still 100% murine. I remember reading something a couple of years ago stating that they were comparable in effectiveness but at the time children’s bodies were understandably more accepting of ch14.18 due to it being mostly human. Now that 3F8 is humanized I’m not sure…

(Sam Saffron) #3

I never knew that happened, any details on when that happened and what impact it made? Maybe we should reach out to MSK for some more info?

(Rochelle Paterson) #4

I wish I knew more about 3f8. Hopefully someone else on this forum can provide more insight. When Rea was inpatient, we just read so many positive things about monoclonal antibodies (in general) increasing survival rates, so we trusted our hospital when they offered her ch14.18 after frontline tx, and I’m sure MSKCC families did the same when offered 3f8. From what I’ve read, they’ve both proven to be effective. Rea had the standard immunotherapy cocktail of ch14.18, IL-2, GM-CSF, and Accutane. I hope you get all the answers you’re looking for. :slight_smile:

(Kyle Matthews) #5

Here’s Sloan’s page on 3F8:

Looks like their Phase I trial of Hu3F8 (Humanized 3F8) first went into in 2011:

(Sam Saffron) #6

There is a lot of informations there!

Key points:

  • Recruiting

  • hu3F8 appears to only be available for relapse or refractory NB

  • Tumour must be GD2 positive

  • Cycles are 21 days and can be repeated up to a total of 12 cycles

  • Prior treatment with 3F8 or ch14.18 is allowed provided conditions are met

  • Trial only available at MSK

(Sam Saffron) #7

Looks like ANR will have some more info about this:

Phase I study of anti-GD2 humanized 3F8 (hu3F8) monoclonal antibody (MAb) plus GM-CSF: High dosing and major responses in patients with resistant high-risk neuroblastoma (HR-NB) (#27)

Brian H Kushner 1 , Irene Y Cheung 1 , Ellen M Basu 1 , Shakeel Modak 1 , Stephen S Roberts 1 , Yi Feng 1 , Hoa Tran 1 , Nai Kong V Cheung 1
Memorial Sloan Kettering Cancer Center, New York, NEW YORK, United States
Background: Strategies to improve anti-GD2 immunotherapy include: avoiding sensitization (as can occur with murine and chimeric MAbs); augmenting affinity of MAb for Fc-receptor, thereby enhancing antibody-dependent cellular cytotoxicity (ADCC); and reducing pain associated with complement activation. Murine-3F8 anti-GD2 MAb is active against HR-NB but hu3F8 may be preferable because it has significantly greater ADCC and less complement activity in vitro. GM-CSF is well tolerated clinically and increases ADCC.

Methods: In a phase I study (NCT01757626) (opened in 12/2012), patients with resistant HR-NB receive cycles of hu3F8+GM-CSF monthly x4 in the absence of human antihuman antibody (HAHA) and then with 1-to-2-month intervals if clinically indicated. MAb dosing follows the standard 3+3 design, beginning at 0.9mg/cycle, to identify the maximum-tolerated dosage (MTD) (assessed in first cycle). MAb is infused intravenously (30”) on Mon-Wed-Fri (i.e., 3 days/cycle). Daily GM-CSF is administered subcutaneously 5 days pre-hu3F8 through the last day of hu3F8. After cycle 2, hu3F8 can be increased to the highest dosage level that completed dose-limiting toxicity assessment.

Results: At study entry, the 51 patients enrolled to date were 2.4-31.3 (median 6.8) years old and 0.6-8.9 (median 3.2) years from HR-NB diagnosis. Pharmacokinetic studies showed dose-dependent increases in peak serum concentration; terminal half-life was >3 days. Treatment has been outpatient without unexpected acute, late, or cumulative toxicities, even in patients who received >10 cycles. MTD has not been reached. Current hu3F8 dosage is 9mg/kg/cycle. HAHA developed post-cycle 1 in only 1/9 patients who had no prior treatment with any anti-GD2 MAb. Major responses and prolonged progression-free survival have been observed at all dosage levels.

Conclusions: Modest toxicity allows high dosing of hu3F8 (>2.5x dosage of murine-3F8 and ch14.18) > which, in addition to powerful in vitro cytotoxic features, can account for the notable anti-NB activity of hu3F8+GM-CSF. Pharmacokinetic studies support the alternate-day schedule.


The thing that sticks out to me is they can achieve significantly higher (2.5x) dosing with hu3F8 than they do with ch14.18.